TAFII250

a transcription toolbox

David A. Wassarman1 and Frank Sauer2,*

1 National Institutes of Health, National Institute of Child Health and Human Development, Cell Biology and Metabolism Branch, Building 18T, Room 101, Bethesda, MD 20892, USA
2 Zentrum fur Molekulare Biologie der Universtät Heidelberg (ZMBH), Im Neunheimer Feld 282, Heidelberg 69120, Germany
* Author for correspondence (e-mail: f.sauer{at}mail.zmbh.uni-heidelberg.de )


    SUMMARY
 Top
 SUMMARY
 Introduction
 TAFII250 is a broadly...
 TAFII250 is not the...
 TAFII250 function is regulated...
 TAFII250 binds to core...
 TAFII250 post-translationally...
 Conclusions and perspectives: a...
 REFERENCES
 
Activation of RNA-polymerase-II-dependent transcription involves conversion of signals provided by gene-specific activator proteins into the synthesis of messenger RNA. This conversion requires dynamic structural changes in chromatin and assembly of general transcription factors (GTFs) and RNA polymerase II at core promoter sequence elements surrounding the transcription start site of genes. One hallmark of transcriptional activation is the interaction of DNA-bound activators with coactivators such as the TATA-box binding protein (TBP)-associated factors (TAFIIs) within the GTF TFIID. TAFII250 possesses a variety of activities that are likely to contribute to the initial steps of RNA polymerase II transcription. TAFII250 is a scaffold for assembly of other TAFIIs and TBP into TFIID, TAFII250 binds activators to recruit TFIID to particular promoters, TAFII250 regulates binding of TBP to DNA, TAFII250 binds core promoter initiator elements, TAFII250 binds acetylated lysine residues in core histones, and TAFII250 possesses protein kinase, ubiquitin-activating/conjugating and acetylase activities that modify histones and GTFs. We speculate that these activities achieve two goals - (1) they aid in positioning and stabilizing TFIID at particular promoters, and (2) they alter chromatin structure at the promoter to allow assembly of GTFs - and we propose a model for how TAFII250 converts activation signals into active transcription.

Key words: TAFII250, TFIID, Histone acetyltransferase, Kinase, Ubiquitination, Chromatin, Transcription


    Introduction
 Top
 SUMMARY
 Introduction
 TAFII250 is a broadly...
 TAFII250 is not the...
 TAFII250 function is regulated...
 TAFII250 binds to core...
 TAFII250 post-translationally...
 Conclusions and perspectives: a...
 REFERENCES
 
The expression of thousands of genes in eukaryotic cells is regulated at the level of transcription. This regulation involves the orchestrated interplay of chromatin-packaged genes with multiprotein complexes that control chromatin dynamics, transcription initiation and transcription elongation. The inability of general transcription factors (GTFs) to access chromatin, DNA wrapped around core histones H2A, H2B, H3 and H4 in repeating subunits called nucleosomes, implies that a requisite step in transcription initiation is the alteration of chromatin structure (Wolffe, 1998Go). Two general classes of complex/enzyme have been implicated in chromatin-altering events: ATP-dependent nucleosome-remodeling complexes (e.g. SWI/SNF, RCS, ACS, CHRAC, NURF, and Mi-2/ NURD) and histone-modifying enzymes (e.g. histone acetyltransferases (HATs) and histone deacetylases (HDACs); Strahl and Allis, 2000Go; Vignali et al., 2000Go). Although the order of action of chromatin-remodeling/modifying complexes during transcriptional activation may be gene specific, their interdependent activities appear to precede and facilitate binding of TFIID, which, along with TFIIB, are the only components of the preinitiation complex (PIC) that can bind specifically to core promoter DNA (Lagrange et al., 1998Go; Cosma et al., 1999Go; Krebs et al., 1999Go; Agalioti et al., 2000Go).

TAFII250 is one of 10-12 TATA-binding protein (TBP)-associated factors (TAFIIs) that are complexed with TBP in TFIID (Albright and Tjian, 2000Go; Aoyagi and Wassarman, 2000Go). Binding of TFIID to a core promoter surrounding the transcription start site of a gene nucleates assembly of the PIC, which contains RNA polymerase II (RNA pol II) and GTFs TFIIA, TFIIB, TFIIE, TFIIF and TFIIH (Orphanides et al., 1996Go; Hampsey, 1998Go). The nucleating function of TFIID is thought to comprise several distinct activities: (1) activator-dependent recognition of core promoter DNA sequence elements; (2) the generation of a chromatin environment that is favorable to PIC assembly and transcription initiation; and (3) structural modification of GTFs to facilitate PIC assembly and transcription initiation. TAFII250 contributes to each of these TFIID activities. Recent excitement about TAFII250 stems from its involvement in regulating the association of TFIID with the core promoter initiator element and its intrinsic enzymatic activities that post-translationally modify GTFs and histones. Here, we review recent studies of TAFII250 and suggest a model for how TAFII250 activities contribute to gene-specific transcriptional activation in the context of chromatin.


    TAFII250 is a broadly acting regulator of transcription
 Top
 SUMMARY
 Introduction
 TAFII250 is a broadly...
 TAFII250 is not the...
 TAFII250 function is regulated...
 TAFII250 binds to core...
 TAFII250 post-translationally...
 Conclusions and perspectives: a...
 REFERENCES
 
TAFII250 is an essential protein in yeast, fruit flies, hamster cell lines and probably all eukaryotic organisms (Talavera and Basilico, 1977Go; Nishimoto et al., 1982Go; Poon et al., 1995Go; Wassarman et al., 2000Go). Homologs are designated TAFII130 and TAFII145 in yeast, TAFII230 and TAFII250 in Drosophila, and TAFII250 and cell cycle gene 1 (CCG1) in mammals (Aoyagi and Wassarman, 2000Go). Here, we use TAFII145 and TAFII250 to refer to the yeast and metazoan proteins, respectively. Inactivation of TAFII145 in yeast or TAFII250 in hamster cell lines results in arrest in G1 phase of the cell cycle, and null mutations in Drosophila TAFII250 result in lethality late in embryogenesis or early in larval development (Talavera and Basilico, 1977Go; Nishimoto et al., 1982Go; Walker et al., 1996Go; Wassarman et al., 2000Go). Furthermore, homozygous mutant clones of TAFII250 cannot be generated in Drosophila, which suggests that it has a role in cell proliferation or cell survival (Wassarman et al., 2000Go).

The essential nature of TAFII250 can be attributed to its broad requirement during RNA-pol-II-dependent transcription. In Drosophila, TAFII250 is expressed in all nuclei and binds to a large number of euchromatic sites on polytene chromosomes (Rabenstein et al., 1999Go; Wassarman et al., 2000Go). In yeast, genome-wide microarray analysis indicates that expression of 14-27% of RNA-pol-II-transcibed genes is downregulated >twofold upon TAFII145 inactivation (Lee et al., 2000Go). Finally, in ts13 hamster cells that harbor a temperature-sensitive allele of TAFII250, similar analysis indicates that the transcription of 18% of genes transcribed by RNA pol II is affected >twofold at the non-permissive temperature (O'Brien and Tjian, 2000Go). As anticipated, given the phenotype of TAFII250 mutants, many genes showing TAFII250-dependent expression encode proteins that are involved in cell cycle regulation and growth control (Wang and Tjian, 1994Go; Walker et al., 1997Go; Lee et al., 2000Go; O'Brien and Tjian, 2000Go).

TAFII250 could play a more extensive role in transcription than these studies predict, since temperature-sensitive mutations might not inactivate all TAFII250 functions (Dikstein et al., 1996Go; Dunphy et al., 2000Go; Lee et al., 2000Go; Tsukihashi et al., 2000Go). There is considerable disagreement among researchers about the extent to which TAFIIs in general are required for RNA pol II transcription (Moqtaderi et al., 1996Go; Walker et al., 1996Go; Komarnitsky et al., 1999Go; Lee et al., 2000Go). Part of this controversy results from the fact that a subset of TAFIIs are components of other transcriptional regulatory complexes, which makes it difficult to resolve the contribution of a TAFII to TFIID activity (Bell and Tora, 1999Go). However, even in the case of TAFII250, which appears to be unique to TFIID, this is a difficult question to address, since there are factors that can bypass a requirement for some TAFII250 functions.

A growing list of factors can rescue cell cycle arrest of, or block apoptosis of, ts13 or tsBN462 hamster cells, which contain an identical glycine-to-aspartate missense mutation in TAFII250 (Hayashida et al., 1994Go). This list includes viral proteins (simian virus 40 (SV40) large T antigen (Damania and Alwine, 1996Go), hepatitis B virus pX (Haviv et al., 1998Go), human cytomegalovirus (HCMV) immediate-early (IE) proteins IEP86 and IEP72 (Lukak and Alwine, 1999), and human papilloma virus (HPV) 16 E7 (Sekiguchi et al., 1999Go)) and cellular proteins (E2F-1 (Sekiguchi et al., 1999Go), CIITA (Raval et al., 2001Go) and D-type cyclins (Sekiguchi et al., 1999Go)). Two distinct mechanisms are involved: overexpression of viral proteins or CTIIA rescues cells by activating TAFII250-dependent promoters in the absence of functional TAFII250, whereas overexpression of E2F-1 and D-type cyclins rescues cells by providing the downstream targets of TAFII250 activity. SV40 large T antigen, HCMV IE and CIITA proteins bind to TAFIIs in vitro and in vivo, and mutations that affect TAFII interactions are unable to rescue the ts13 or tsBN462 transcriptional defects (Damania and Alwine, 1996Go; Mahanta et al., 1997Go; Lukak and Alwine, 1999). Furthermore, rescue by CTIIA depends on its acetyltransferase activity (Raval et al., 2001Go). Since TAFII250 acetyltransferase activity is impaired in tsBN462 cells (discussed below), this suggests that CIITA substitutes for TAFII250 by performing two of its functions: association with TFIID and acetylation of proteins. Thus, other viral and cellular proteins that rescue ts13 or tsBN462 cell defects and associate with TFIID might also be acetyltransferases or affiliate with an acetyltransferase.


    TAFII250 is not the only scaffold for TFIID in vivo
 Top
 SUMMARY
 Introduction
 TAFII250 is a broadly...
 TAFII250 is not the...
 TAFII250 function is regulated...
 TAFII250 binds to core...
 TAFII250 post-translationally...
 Conclusions and perspectives: a...
 REFERENCES
 
The TFIID complex is held together by TAFII-TAFII and TAFII-TBP interactions. In particular, Drosophila TAFII250 engages in strong interactions with TBP, TAFII30{alpha}, TAFII30ß, TAFII60, TAFII80, TAFII110 and TAFII150 (Chen et al., 1994Go; Fig. 1). Immobilized TAFII250 can serve as a scaffold for assembly of TFIID subcomplexes and holo-TFIID from recombinant subunits, which suggests that assembly and integrity of TFIID are dependent on TAFII250. Accordingly, inactivation of TAFII250 in yeast leads to degradation of other TFIID subunits (Walker et al., 1996Go). However, inactivation of all TAFIIs tested to date results in degradation of other TAFIIs, which suggests that every TAFII is necessary for the integrity of TFIID in vivo (Walker et al., 1996Go; Michel et al., 1998Go; Moqtaderi et al., 1998Go).



View larger version (14K):
[in this window]
[in a new window]
 
Fig. 1. A schematic diagram of metazoan TAFII250. Locations of enzymatic domains (N-terminal kinase domain (NTK), C-terminal kinase domain (CTK), histone acetyltransferase domain (HAT), and ubiquitin-activating/conjugating domain (E1/E2)) and bromodomains (Bromo) are indicated within the linear TAFII250 protein. Substrates for the enzymatic activities are indicated above the TAFII250 protein, and interacting proteins are indicated below the protein. Substrates and interacting partners are abbreviated as follows: TFIIA (A), TFIIE (E), TFIIF (F), TATA-binding protein (TBP), retinoblastoma protein (RB), HIV Tat (TAT) and TFIIF{alpha} (RAP74).

 


    TAFII250 function is regulated by activators
 Top
 SUMMARY
 Introduction
 TAFII250 is a broadly...
 TAFII250 is not the...
 TAFII250 function is regulated...
 TAFII250 binds to core...
 TAFII250 post-translationally...
 Conclusions and perspectives: a...
 REFERENCES
 
How do TAFIIs increase the rate of transcription initiation? The initial finding that TFIID, but not TBP, can mediate activator-directed transcription in a reconstituted RNA pol II system indicated that one function of TAFIIs is to respond to enhancer-bound activators (Pugh and Tjian, 1990Go; Dynlacht et al., 1991Go). In the case of TAFII250, activator interactions increase promoter occupancy of TFIID (i.e. recruitment) and modulate TAFII250 regulatory and enzymatic activities (i.e. regulation). Physical interactions between TAFII250 and activators are a critical component of these mechanisms. TAFII250 binds activators (e.g. HIV Tat (Weissman et al., 1998Go), adenovirus E1A (Geisberg et al., 1995Go), Herpes simplex virus type 1 ICP4 (Carozza and DeLuca, 1996) and JUN (Lively et al., 2001Go)), and other transcriptional regulators (retinoblastoma tumor suppressor protein RB (Seigert and Robbins, 1999), the MDM2 proto-oncogene (Leveillard and Wasylyk, 1997Go) and cyclin D (Seigert et al., 2000)) (Fig. 1).

Distinct lines of evidence point to a mechanism by which activators bind to TAFII250 to tether TFIID to particular promoters (Fig. 2). (1) The region of ICP4 required for transcriptional activation is also required for TAFII250 association (Carrozza and DeLuca, 1996Go). (2) Gene-specific promoter occupancy of TAFII145 in yeast is elevated in response to an activation signal and is reduced after removal of enhancer sites (Kuras et al., 2000Go; Li et al., 2000Go). (3) Enhancers can confer TAFII250 dependence on promoters that are normally TAFII250 independent (Wang et al., 1997Go). Once recruited to a promoter, TAFII250 could participate in PIC assembly by binding to the RAP74 subunit (also designated TFIIF{alpha}) of TFIIF, as suggested by the finding that TAFII250 mutants that fail to interact with RAP74 are unable to rescue the ts13 cell cycle defect (Ruppert and Tjian, 1995Go). Tethering of TFIID to particular genes through activator-TAFII250 binding is advantageous because TFIID is limiting in cells (Walker et al., 1996Go). The importance of TAFII250 interactions with both activators and GTFs argues that TAFII250 functions as a classically defined coactivator that bridges activators to PIC assembly.



View larger version (37K):
[in this window]
[in a new window]
 
Fig. 2. A four-step model for how TAFII250 contributes to transcriptional activation. In each step, the panel on the left depicts the general event and the panel on the right depicts the specific contribution of TAFII250 to the event. Activators are denoted by a red circle labeled A; TFIIA is denoted by a green oval labeled A; TFIIE is denoted by a green circle labeled E; TFIIF is denoted by a blue circle labeled F; histones are labeled H1, H2A, H2B, H3 or H4; and TFIID is denoted by a collection of objects labeled 250, 150 and TBP. The balance of the general transcription machinery, which is not specifically identified, is indicated by a collection of objects labeled GTM.

 

There is also ample support for a mechanism in which activators modify TAFII250 activities to enhance formation or stability of the PIC on promoter DNA (Fig. 2). Competitive interplay between activators and TAFII250 could control binding of TFIID to core promoters. The N-terminus of TAFII250 binds to the DNA-binding surface of TBP and inhibits TBP-DNA interactions (Kotani et al., 1998Go). However, acidic activators, JUN and TFIIA compete with TAFII250 for binding to TBP, thus altering the DNA-binding properties of TFIID (Kokubo et al., 1998Go; Ozer et al., 1998Go; Kotani et al., 2000Go; Lively et al., 2001Go). Moreover, some repressors inhibit TAFII250 enzymatic activities (discussed below) that may promote PIC assembly by modifying the structure of GTFs and chromatin. Binding of HIV Tat, an activator and repressor of viral gene transcription, to TAFII250 inhibits TAFII250 HAT activity (Weissman et al., 1998Go). Similarly, binding of RB to TAFII250 inhibits TAFII250 N-terminal kinase activity (Siegert and Robbins, 1999Go; Solow et al., 2001Go). In contrast, E1A and cyclin D1 suppress the TAFII250-kinase-inhibitory effect of RB (Siegert et al., 2000Go). Thus, regulation of TAFII250 activities by interactions with activators and GTFs is integral to the process of transcriptional activation.


    TAFII250 binds to core promoter initiator sequences
 Top
 SUMMARY
 Introduction
 TAFII250 is a broadly...
 TAFII250 is not the...
 TAFII250 function is regulated...
 TAFII250 binds to core...
 TAFII250 post-translationally...
 Conclusions and perspectives: a...
 REFERENCES
 
DNA-crosslinking experiments have revealed that TAFII250 intimately contacts the core promoter initiator element both in TATA-box-containing and TATA-less core promoters (Purnell et al., 1994Go; Sypes and Gilmour, 1994Go; Verrijzer et al., 1995Go; Wu et al., 2001Go; Fig. 2). The initiator (Inr) is a conserved sequence element that encompasses the start site of transcription and can direct accurate transcription initiation in the absence of a TATA box (Smale, 1997Go). A role for TAFIIs in recognizing the Inr was suggested by the finding that TFIID containing a TBP subunit that cannot bind to DNA cannot function on TATA-only promoters but can support transcription from TATA-less, Inr-containing promoters (Martinez et al., 1994Go). Mutational analysis suggests that a region C-terminal to the HAT domain of yeast TAFII145 is required for promoter binding in vivo (Mencia and Struhl, 2001Go). In vitro, recombinant TAFII250-TAFII150, TBP-TAFII250 and TBP-TAFII250-TAFII150 complexes efficiently bind Inr-containing promoters (Chen et al., 1994Go; Verrijzer et al., 1995Go). Moreover, a TAFII250-TAFII150 complex can support Inr-mediated transcription and specifically binds sequences that match the Inr consensus sequence from a pool of random sequence oligonucleotides (Verrijzer et al., 1995Go; Chalkley and Verrijzer, 1999Go). These results imply that TAFII250, together with TAFII150, mediates binding of TFIID to the Inr and that TBP is dispensable for this activity. This hypothesis is further supported by the identification of TBP-free TFIID complexes from mammalian cells that support transcription from TATA-less and TATA-containing promoters that contain Inr elements (Wieczorek et al., 1998Go).

Analysis of core promoters of genes whose expression is affected by TAFII250 mutations does not clarify the role of the TATA element in specifying TAFII250 dependence. Some TAFII250-dependent promoters contain a nonconsensus TATA element, whereas others contain a consensus TATA element (Moqtaderi et al., 1996Go; Shen and Green, 1997Go). Insertion of a canonical TATA element into a TATA-less promoter can bypass a dependence on TAFII145, but mutation of a weak TATA element to the consensus sequence does not change the requirement for TAFII145 (Shen and Green, 1997Go; Tsukihashi et al., 2000Go). Thus, there appears to be a sophisticated code composed of contributions from TATA and Inr core promoter elements that specifies TAFII250 dependence.


    TAFII250 post-translationally modifies histones and GTFs
 Top
 SUMMARY
 Introduction
 TAFII250 is a broadly...
 TAFII250 is not the...
 TAFII250 function is regulated...
 TAFII250 binds to core...
 TAFII250 post-translationally...
 Conclusions and perspectives: a...
 REFERENCES
 
Functional characterization of TFIID and searches for enzymes that post-translationally modify histones have demonstrated that TAFII250 possesses protein kinase, HAT, and ubiquitin-activating and -conjugating enzymatic activities (Figs 1, 2). Interestingly, TAFII250 does not have significant sequence similarity to other members of these enzyme families, which raises the possibility that other TAFIIs, and other proteins in general, possess enzymatic domains that remain unidentified because they do not conform to defined primary sequence motifs.

TAFII250 is a bipartite protein kinase
TAFII250 contains two independent serine/threonine protein kinase domains: one at the N-terminus (NTK) and the other at the C-terminus (CTK; Dikstein et al., 1996Go; O'Brien and Tjian, 1998Go; Fig. 1). Kinase activity has been demonstrated in vitro for the Drosophila, human and yeast proteins. Yeast is unusual in that the kinase domains reside in two separate proteins. TAFII145 and Bromodomain factor 1 (Bdf1) contain the NTK and CTK, respectively (Mantangkasonbut et al., 2000).

The TAFII250 NTK and CTK domains autophosphorylate, and the NTK domain transphosphorylates RAP74 and the large subunit of TFIIA (TFIIA-L) in vitro (Dikstein et al., 1996Go; Solow et al., 2001Go). RAP74 and TFIIA are reasonable candidates as substrates for TAFII250 kinase activity in vivo: endogenous RAP74 is hyperphosphorylated; dephosphorylation of RAP74 reduces its ability to support transcription elongation in vitro; and phosphorylation of TFIIA stimulates TFIIA-TBP-TATA-element complex formation in vitro (Kitajima et al., 1994Go; Solow et al., 2001Go; Fig. 2). Autophosphorylation by TAFII250 might also play a regulatory role in transcription, as has been shown for TFIIF (Rossignol et al., 1999Go). Despite the lack of definitive substrates, it is clear that kinase activity is required in vivo, because a recombinant TAFII250 protein that lacks the NTK domain cannot rescue ts13 phenotypes (O'Brien and Tjian, 1998Go; O'Brien and Tjian, 2000Go). Moreover, deletion of the CTK in Drosophila results in lethality (V. Jo, J. G. Shanklin, E. M. Schlag and D.A.W., unpublished).

TAFII250 is a histone acetyltransferase and binds to acetylated histones
Mizzen et al. using an in-gel activity assay, showed that TAFII250 has HAT activity (Mizzen et al., 1996Go). The HAT domain maps to the central, most conserved portion of metazoan TAFII250 and the C-terminal portion of yeast TAFII145 (Fig. 1). Many studies have established a correlation between acetylation of highly conserved lysine residues in the N-terminal tails of histones and transcriptional activation (Strahl and Allis, 2000Go). One model to explain how histone acetylation affects gene expression proposes that the extent of chromatin condensation is directly related to the level of histone acetylation. Accordingly, hyperacetylation reduces the affinity of histone tails for DNA, resulting in less compact chromatin and increased accessibility of transcription factors to DNA.

In vitro, Drosophila TAFII250 acetylates free histones and nucleosomal histones weakly, relative to yeast HAT1 and human P/CAF (Mizzen et al., 1996Go; Wassarman et al., 2000Go). Lys14 of histone H3 is the preferred site of acetylation, although other lysine residues in H3 and H4 are good substrates for TAFII250 (Mizzen et al., 1996Go). TAFII250 also acetylates TFIIEß and TFIIF in vitro (Imhof et al., 1997Go) Evidence for the in vivo importance of TAFII250 HAT activity comes from ts13 and tsBN462 cells. The ability of mutant TAFII250 to acetylate histones in vitro is temperature sensitive, suggesting that the enzymatic activity is compromised in ts13 cells at the nonpermissive temperature and that cell cycle and transcriptional defects observed at the nonpermissive temperature result from reduced HAT activity (Dunphy et al., 2000Go).

Although histones and GTFs are substrates for TAFII250 acetyltransferase activity in vitro, it is unclear whether they are transcriptionally relevant substrates. Two lines of evidence indicate that histones might not be relevant substrates in vitro: (1) transcriptional activation is temperature sensitive from non-chromatin templates in ts13 cells extracts; and (2) inhibition of TAFII250 acetyltransferase activity by HIV Tat represses transcription from non-chromatin templates in HeLa cell extracts (Wang and Tjian, 1994Go; Weissman et al., 1998Go). Thus, the TAFII250 acetyltransferase activity is necessary in vitro even in the absence of histones. Furthermore, TFIIEß and TFIIF might not be relevant substrates in vitro, because no proteins are acetylated in reconstituted transcription reactions containing purified GTFs (including TFIID, TFIIEß and TFIIF), RNA pol II and an activator (Galasinski et al., 2000Go). However, it remains an open question whether GTFs and histones are acetylated by TAFII250 in vivo. Acetylation of histones by TAFII250 in vivo might produce a localized change in chromatin structure to enhance accessibility and binding of TFIID and other PIC components (Fig. 2).

In addition to acetylating proteins, TAFII250 binds to multiply acetylated histones through two tandem bromodomains located in the C-terminal region of the protein (Jacobson et al., 2000Go; Fig. 1). The bromodomain is an ~120-residue motif present in a variety of proteins that associate with chromatin (Jeanmougin et al., 1997Go). The TAFII250 double bromodomain (DBD) binds most tightly to histone H4 acetylated at lys5 and lys12 (Jacobson et al., 2000Go). This is consistent with the crystal structure of the DBD, which shows that the binding pockets for acetyllysine span a distance equivalent to seven residues. Therefore, the TAFII250 bromodomains may target TFIID to chromatin-packaged promoters (Fig. 2).

TAFII250 is a ubiquitin-activating/conjugating enzyme
Most recently, TAFII250 has been demonstrated to mediate monoubiquitination of histone H1, a linker histone that binds to DNA between adjacent nucleosomes (Crane-Robinson, 1999Go; Pham and Sauer, 2000Go). In vitro, monoubiquitination requires the sequential activity of ubiquitin-activating (E1) and ubiquitin-conjugating (E2) enzymes (Ciechanover et al., 2000Go). TAFII250 contains both of these activities: it becomes covalently linked, via a thioester bond, to ubiquitin in an ATP-dependent manner (E1 activity), and it transfers activated ubiquitin to histone H1 via an isopeptide bond (E2 activity; Pham and Sauer, 2000Go). The E1 and E2 activities of Drosophila and human TAFII250 reside in the central region of the protein (Fig. 1). Most intriguingly, this region is absent from yeast TAFII145 and Bdf1, and, whereas a histone-H1-like protein (HHO1) has been reported in yeast, it is not known whether it is functionally homologous to metazoan H1 proteins (Ushinsky et al., 1997Go).

Mutations in Drosophila TAFII250 that impair histone H1 ubiquitination activity in vitro and in vivo were isolated in a genetic screen for genes that modulate the ability of the Ras GTPase to specify cell fates (Karim et al., 1996Go; Wassarman et al., 2000Go). Gene targets for TAFII250 in Ras signaling pathways have not been identified, but TAFII250 mutations do affect transcription in the Drosophila embryo, reducing the expression of Dorsal and Caudal target genes (Pham and Sauer, 2000Go; A.-D. Pham and F.S., unpublished). It is unclear how monoubiquitination of histone H1 by TAFII250 mediates transcription. One attractive model, based on the ability of H1 to facilitate the folding of nucleosomal arrays into higher-order structures, is that ubiquitination changes the chromatin-binding properties of H1 and thereby destabilizes both local and higher-order chromatin structures and alters core histone-DNA interactions (Crane-Robinson, 1999Go; Mizzen and Allis, 2000Go; Fig. 2). Indeed, binding of histone H1 to chromatin is highly dynamic in living cells, and modulation of H1 binding activity is thought to be an important step in regulating access of the transcriptional machinery to DNA (Lever et al., 2000Go; Misteli et al., 2000Go).

While TAFII250 does not require an E3 ubiquitin-ligase to monoubiquitinate histone H1 in vitro, it is possible that it utilizes one to ubiquitinate other proteins in vivo. An excellent candidate for this enzyme is the MDM2 ubiquitin ligase, whose binding to TAFII250 correlates with transcriptional activation (Honda et al., 1997Go; Leviellard and Wasylyk, 1997). In vivo, MDM2 may target the E1 and E2 activities of TAFII250 to proteins such as p53 (Buschmann et al., 2000Go).


    Conclusions and perspectives: a model for the role of TAFII250 during transcriptional activation
 Top
 SUMMARY
 Introduction
 TAFII250 is a broadly...
 TAFII250 is not the...
 TAFII250 function is regulated...
 TAFII250 binds to core...
 TAFII250 post-translationally...
 Conclusions and perspectives: a...
 REFERENCES
 
Detailed in vitro and in vivo analyses have uncovered a plethora of TAFII250 activities that together underscore the importance of TAFII250 as a regulator of RNA pol II transcription. On the basis of these studies, we propose the following model for how TAFII250 regulates gene expression (Fig. 2).

  1. The signal instructing TFIID where to bind the genome probably comes from activators that bind both cis-regulatory regions of target genes and TFIID to recruit TFIID to particular genes. TAFII250 plays a fundamental role in this recruitment process, serving as a binding partner for activators and as a scaffold for other TAFII subunits of TFIID. Furthermore, activator-TAFII250 interactions might regulate the timing or the substrate specificity of the TAFII250 enzymatic activities.
  2. Once recruited to a gene, TFIID recognizes and binds to the core promoter. TAFII250 plays a dual role in this process, regulating TBP-DNA interactions and, with the assistance of TBP and/or TAFII150, directly recognizing and binding to Inr elements. The arsenal of TAFII250 enzymatic functions may be employed at this point to provide accessibility to nucleosome-embedded core promoters. Requirements for individual TAFII250 activities could be gene specific, since impairment of NTK or HAT activity affects the expression of different genes (O'Brien and Tjian, 2000Go).
  3. TAFII250-mediated monoubiquitination of histone H1 and acetylation of histones H2B, H3 and H4 might elicit dynamic changes in chromatin structure that facilitate binding of TFIID.
  4. Binding of the TAFII250 double bromodomain to acetylated histones might stabilize the interaction of TFIID with nucleosomes during the process of chromatin remodeling.
  5. Once bound to DNA, TFIID nucleates assembly of the PIC at the start site of transcription. TAFII250-mediated structural changes within chromatin could allow the interaction of the PIC with DNA that is required for initiation and elongation of transcription.
  6. During or after PIC assembly, TAFII250 could modify TFIIF{alpha} and TFIIA-L by phosphorylation and TFIIEß and TFIIF by acetylation, thereby regulating the contribution of TFIIA, TFIIE and TFIIF to transcription initiation and elongation.

In summary, this simplistic model describes how individual tools contained within a TAFII250 `toolbox' contribute to the conversion of activation signals received by TFIID into the enzymatic synthesis of messenger RNA. We anticipate that the model will undergo numerous refinements as in vivo substrates for TAFII250 activities are defined, the molecular consequences of these modifications are determined, and high-resolution structures of TAFII250, TFIID and the PIC are solved (Andel et al., 1999Go).


    ACKNOWLEDGMENTS
 
This work was supported by the Intramural Program in the National Institute of Child Health and Human Development (D.A.W.) and the DFG (F.S.). We thank R. Kamakaka, L. Pile and an anonymous reviewer for comments that greatly improved the manuscript.


    REFERENCES
 Top
 SUMMARY
 Introduction
 TAFII250 is a broadly...
 TAFII250 is not the...
 TAFII250 function is regulated...
 TAFII250 binds to core...
 TAFII250 post-translationally...
 Conclusions and perspectives: a...
 REFERENCES
 

Agalioti, T., Lomvardas, S., Parekh, B., Yie, J., Maniatis, T. and Thanos, D. (2000). Ordered recruitment of chromatin modifying and general transcription factors to the INF-ß promoter. Cell 103,667 -678.[Medline]

Albright, S. R. and Tjian, R. (2000). TAFs revisited: more data reveal new twists and confirm old ideas. Gene 242,1 -13.[Medline]

Andel, F., III, Ladurner, A. G., Inouye, C., Tjian, R. and Nogales, E. (1999). Three-dimensional structure of the human TFIID-IIA-IIB complex. Science 286,2153 -2156.[Abstract/Free Full Text]

Aoyagi, N. and Wassarman, D. A. (2000). Genes encoding Drosophila melanogaster RNA Polymerase II general transcription factors: diversity in TFIIA and TFIID components contributes to gene-specific transcriptional regulation. J. Cell Biol. 150,F45 -F49.[Abstract/Free Full Text]

Bell, D. and Tora, L. (1999). Regulation of gene expression by multiple forms of TFIID and TAFII-containing complexes. Exp. Cell Res. 246, 11-19.[Medline]

Buschmann, T., Fuchs, S. Y., Lee, C. G., Pan, Z. Q. and Ronai, Z. (2000). SUMO-1 modification of MDM2 prevents its self-ubiquitination and increases MDM2 ability to ubiquitinate p53. Cell 101,753 -762.[Medline]

Carrozza, M. J. and DeLuca, N. A. (1996). Interaction of the viral activator protein ICP4 with TFIID through TAF250. Mol. Cell. Biol. 16,3085 -3093.[Abstract]

Chalkley, G. E. and Verrijzer, C. P. (1999). DNA binding site selection by RNA polymerase II TAFs: a TAFII250-TAFII150 complex recognizes the initiator. EMBO J. 18,4835 -4845.[Abstract/Free Full Text]

Chen, J.-L., Attardi, L. D., Verrijzer, C. P., Yokomori, K. and Tjian, R. (1994). Assembly of recombinant TFIID reveals different coactivator requirement for distinct transcriptional activators. Cell 79,93 -105.[Medline]

Ciechanover, A., Orian, A. and Schwartz, A. L. (2000). Ubiquitin-mediated proteolysis: biological regulation via destruction. BioEssays 22,442 -451.[Medline]

Cosma, M. P., Tanaka, T. and Nasmyth, K. (1999). Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle and developmentally regulated promoter. Cell 97,299 -311.[Medline]

Crane-Robinson, C. (1999). How do linker histones mediate differential gene expression? BioEssays 21,367 -371.[Medline]

Damania, B. and Alwine, J. C. (1996). TAF-like function of SV40 large T antigen. Genes Dev. 10,1369 -1381.[Abstract]

Dikstein, R., Ruppert, S. and Tjian, R. (1996). TAFII250 is a bipartite protein kinase that phosphorylates the basal transcription factor RAP74. Cell 84,781 -790.[Medline]

Dunphy, E. L., Johnson, T., Auerbach, S. S. and Wang, E. H. (2000). Requirement for TAFII250 acetyltransferase activity in cell cycle progression. Mol. Cell. Biol. 20,1134 -1139.[Abstract/Free Full Text]

Dynlacht, B. D., Hoey, T. and Tjian, R. (1991). Isolation of coactivators associated with the TATA-binding protein that mediate transcriptional activation. Cell 55,563 -576.

Galasinski, S. K., Lively, T. N., Grebe de Barron, A. and Goodrich, J. A. (2000). Acetyl coenzyme A stimulates RNA polymerase II transcription and promoter binding by transcription factor IID in the absence of histones. Mol. Cell. Biol. 20,1923 -1930.[Abstract/Free Full Text]

Geisberg, J. V., Chen, J. L. and Ricciardi, R. P. (1995). Subregions of the adenovirus E1A transactivation domain target multiple components of the TFIID complex. Mol. Cell. Biol. 15,6283 -6290.[Abstract]

Hampsey, M. (1998). Molecular genetics of the RNA polymerase II general transcription machinery. Microbiol. Mol. Biol. Rev. 62,465 -503.[Abstract/Free Full Text]

Haviv, I., Matza, Y. and Shaul, Y. (1998). PX, the HBV-encoded coactivator, suppresses the phenotypes of TBP and TAFII250 mutants. Genes Dev. 12,1217 -1226.[Abstract/Free Full Text]

Hayashida, T., Sekiguchi, T., Noguchi, E., Sunamoto, H., Ohba, T. and Nishimoto, T. (1994). The CCG1/TAFII250 gene is mutated in thermosensitive G1 mutants of the BHK21 cell line derived from golden hamster. Gene 141,267 -270.[Medline]

Honda, R., Tanaka, H. and Yasuda, H. (1997). Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 420,25 -27.[Medline]

Imhof, A., Yang, X. J., Ogryzko, V. V., Nakatani, Y., Wolffe, A. P. and Ge, H. (1997). Acetylation of general transcription factors by histone acetyltransferases. Curr. Biol. 7, 689-692.[Medline]

Jacobson, R. H., Ladkurner, A. G., King, D. S. and Tjian, R. (2000). Structure and function of a human TAFII250 double bromodomain module. Science 288,1422 -1425.[Abstract/Free Full Text]

Jeanmougin, F., Wurtz, J. M., Le Douarin, B., Chambon, P. and Losson, R. (1997). The bromodomain revisited. Trends Biochem. Sci. 22,151 -153.[Medline]

Karim, F. D., Chang, H. C., Therrien, M., Wassarman, D. A., Laverty, T. and Rubin, G. M. (1996). A screen for genes that function downstream of Ras1 during Drosophila eye development. Genetics 143,315 -329.[Abstract/Free Full Text]

Kitajima, S., Chibazakura, T., Yohana, M. and Yasukochi, Y. (1994). Regulation of the human general transcription factor TFIIF by phosphorylation. J. Biol. Chem. 269,29970 -29977.[Abstract/Free Full Text]

Kokubo, T., Swanson, M. J., Nishikawa, J.-I., Hinnebusch, A. G. and Nakatani, Y. (1998). The yeast TAF145 inhibitory domain and TFIIA competitively bind to TATA-binding protein. Mol. Cell. Biol. 18,1003 -1012.[Abstract/Free Full Text]

Komarnitsky, P. B., Michel, B. and Buratowski, S. (1999). TFIID-specific yeast TAF40 is essential for the majority of RNA polymerase II-mediated transcription in vivo. Genes Dev. 13,2484 -2489.[Abstract/Free Full Text]

Kotani, T., Miyake, T., Tsukihashi, Y., Hinnebusch, A. G., Nakatani, Y., Kawaichi, M. and Kokubo, T. (1998). Identification of highly conserved amino-terminal segments of dTAFII230 and yTAFII145 that are functionally interchangeable for inhibiting TBP-DNA interactions in vitro and in promoting yeast cell growth in vivo. J. Biol. Chem. 273,32254 -32264.[Abstract/Free Full Text]

Kotani, T., Banno, K.-I., Ikura, M., Hinnebusch, A. G., Nakatani, Y., Kawaichi, M. and Kokubo, T. (2000). A role of transcriptional activators as antirepressors for the autoinhibitory activity of TATA box binding of transcription factor IID. Proc. Natl. Acad. Sci. USA 97,7178 -7183.[Abstract/Free Full Text]

Krebs, J. E., Kuo, M. H., Allis, C. D. and Peterson, C. L. (1999). Cell cycle-regulated histone acetylation required for expression of the yeast HO gene. Genes Dev. 13,1412 -1421.[Abstract/Free Full Text]

Kuras, L., Kosa, P., Mencia, M. and Struhl, K. (2000). TAF-containing and TAF-independent forms of transcriptionally active TBP in vivo. Science 288,1244 -1248.[Abstract/Free Full Text]

Lagrange, T., Kapanidis, A. N., Tang, H., Reinberg, D. and Ebright, R. H. (1998). New core promoter element in RNA polymerase II-dependent transcription: sequence-specific DNA binding by transcription factor IIB. Genes Dev. 12, 34-44.[Abstract/Free Full Text]

Lee, T. I., Causton, H. C., Holstege, F. C. P., Shen, W.-C., Hannett, N., Jennings, E. G., Winston, F., Green, M. R. and Young, R. A. (2000). Redundant roles for the TFIID and SAGA complexes in global transcription. Nature 405,701 -704.[Medline]

Leveillard, T. and Wasylyk, B. (1997). The MDM2 C-terminal region binds TAFII250 and is required for MDM2 regulation of the cyclin A promoter. J. Biol. Chem. 272,30651 -30661.[Abstract/Free Full Text]

Lever, M. A., Th'ng, J. P. H., Sun, X. and Hendzel, M. J. (2000). Rapid exchange of histone H1.1 on chromatin in living cells. Nature 408,873 -876.[Medline]

Li, X.-Y., Bhaumik, S. R. and Green, M. R. (2000). Distinct classes of yeast promoters revealed by differential TAF recruitment. Science 288,1242 -1244.[Abstract/Free Full Text]

Lively, T. N., Ferguson, H. A., Galasinski, S. K., Seto, A. G. and Goodrich, J. A. (2001). cJun binds the N-terminus of human TAFII250 to derepress RNA polymerase II transcription in vitro. J. Biol. Chem. (in press).

Lukac D. M. and Alwine, J. C. (1999). Effects of human cytomegalovirus major immediate-early proteins in controlling the cell cycle and inhibiting apoptosis: studies with ts13 cells. J. Virol. 73,2825 -2831.[Abstract/Free Full Text]

Mahanta, S. K., Scholl, T., Yang, F.-C. and Strominger, J. L. (1997). Transactivation by CTIIA, the type II bare lymphocyte syndrome-associated factor, requires participation of multiple regions of the TATA box binding protein. Proc. Natl. Acad. Sci USA 94,6324 -6329.[Abstract/Free Full Text]

Matangkasombut, O., Buratowski, R. M., Swilling, N. W. and Buratowski, S. (2000). Bromodomain factor 1 corresponds to a missing piece of yeast TFIID. Genes Dev. 14,951 -962.[Abstract/Free Full Text]

Martinez, E., Chiang, C.-M., Ge, H. and Roeder, R. G. (1994). TAFs in TFIID function through the initiator to direct basal transcription from a TATA-less class II promoter. EMBO J. 13,3115 -3126.[Abstract]

Mencia, M. and Struhl, K. (2001). Region of yeast TAF130 required for TFIID to associate with promoters. Mol. Cell. Biol. 21,1145 -1154.[Abstract/Free Full Text]

Michel, B., Komarnitsky, P. and Buratowski, S. (1998). Histone-like TAFs are essential for transcription in vivo. Mol. Cell 2,663 -673.[Medline]

Misteli, T., Gunjan, A., Hock, R., Bustin, M. and Brown, D. T. (2000). Dynamic binding of histone H1 to chromatin in living cells. Nature 408,877 -881.[Medline]

Mizzen, C. A. and Allis, C. D. (2000). Transcription. New insights into an old modification. Science 289,2290 -2291.[Free Full Text]

Mizzen, C. A., Yang, X.-J., Kokubo, T., Brownell, J. E., Bannister, A. J., Owen-Hughes, T., Workman, J., Wang, L., Berger, S. L. et al. (1996). The TAFII250 subunit of TFIID has acetyltransferase activity. Cell 87,1261 -1270.[Medline]

Moqtaderi, Z., Bai, Y., Poon, D., Weil, P. A. and Struhl, K. (1996). TBP-associated factors are not generally required for transcriptional activation in yeast. Nature 383,188 -191.[Medline]

Moqtaderi, Z., Keaveney, M. and Struhl, K. (1998). The histone H3-like TAF is broadly required for transcription in yeast. Mol. Cell 2, 675-682.[Medline]

Nishimoto, T., Sekiguchi, T., Kai, R., Yamashita, K., Takahashi, T. and Sekiguchi, M. (1982). Large-scale selection and analysis of temperature-sensitive mutants for cell reproduction from BHK cells. Somatic Cell Genet. 8, 811-824.[Medline]

O'Brien, T. and Tjian, R. (1998). Functional analysis of the human TAFII250 N-terminal kinase domain. Mol. Cell 1,905 -911.[Medline]

O'Brien, T. and Tjian, R. (2000). Different functional domains of TAFII250 modulate expression of distinct subsets of mammalian genes. Proc. Natl. Acad. Sci. USA 97,2456 -2461.[Abstract/Free Full Text]

Orphanides, G., Lagrange, T. and Reinberg, D. (1996). The general transcription factors of RNA polymerase II. Genes Dev. 10,2657 -2683.[Medline]

Ozer, J., Mitsouras, K., Zerby, D., Carey, M. and Lieberman, P. M. (1998). Transcription factor IIA derepresses TATA-binding protein (TBP)-associated factor inhibition of TBP-DNA binding. J. Biol. Chem. 273,14293 -14300.[Abstract/Free Full Text]

Pham, A.-D. and Sauer, F. (2000). Ubiquitin-activating/conjugating activity of TAFII250, a mediator of activation of gene expression. Science 289,2357 -2360.[Abstract/Free Full Text]

Poon, D., Bai, Y., Campbell, A. M., Bjorklund, S., Kim, Y. J., Zhou, S., Kornberg, R. D. and Weil, P. A. (1995). Identification and characterization of a TFIID-like multiprotein complex from Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 92,8224 -8228.[Abstract]

Pugh, B. F. and Tjian, R. (1990). Mechanism of transcriptional activation by Sp1: evidence for coactivators. Cell 61,1187 -1197.[Medline]

Purnell, B. A., Emanuel, P. A. and Gilmour, D. S. (1994). TFIID sequence recognition of the initiator and sequences farther downstream in Drosphila class II genes. Genes Dev. 8,821 -829.[Abstract]

Rabenstein, M. D., Zhou, S., Lis, J. T. and Tjian, R. (1999). TATA box-binding protein (TBP)-related factor 2 (TRF2), a third member of the TBP family. Proc. Natl. Acad. Sci. USA 96,4791 -4796.[Abstract/Free Full Text]

Raval, A., Howcroft, T. K., Weissman, J. D., Kirshner, S., Zhu, X.-S., Yokoyama, K., Ting, J. and Singer, D. S. (2001). Transcriptional coactivator, CTIIA, is an acetyltransferase that bypasses a promoter requirement for TAFII250. Mol. Cell 7,105 -115.[Medline]

Rossignol, M., Keriel, A., Staub, A. and Egly, J.-M. (1999). Kinase activity and phosphorylation of the largest subunit of TFIIF transcription factor. J. Biol. Chem. 274,22387 -22392.[Abstract/Free Full Text]

Ruppert, S. and Tjian, R. (1995). Human TAFII250 interacts with RAP74: implication for RNA polymerase II initiation. Genes Dev. 9,2747 -2755.[Abstract]

Sekiguchi, T., Nishimoto, T. and Hunter, T. (1999). Overexpression of D-type cyclins, E2F-1, SV40 large T antigen and HPV17 E7 rescue cell cycle arrest of tsBN462 cells caused by the CCG1/TAFII250 mutation. Oncogene 18,1797 -1806.[Medline]

Shen, W.-C. and Green M. R. (1997). Yeast TAFII145 functions as a core promoter selectivity factor, not a general coactivator. Cell 90,615 -624.[Medline]

Siegert, J. L. and Robbins, P. D. (1999). Rb inhibits the intrinsic kinase activity of TATA-binding protein-associated factor TAFII250. Mol. Cell. Biol. 19,846 -854.[Abstract/Free Full Text]

Siegert, J. L., Rushton, J. J., Sellers, W. R., Kaelin, W. G. and Robbins, P. D. (2000). Cyclin D1 suppresses retinoblastoma protein-mediated inhibition of TAFII250 kinase activity. Oncogene 19,5703 -5711.[Medline]

Smale, S. T. (1997). Transcription initiation from TATA-less promoters within eukaryotic protein-coding genes. Biochim. Biophys. Acta 1351,73 -88.[Medline]

Solow, S., Salunek, M., Ryan, R. and Lieberman, P. M. (2001). TAFII250 phosphorylates human TFIIA on serine residues important for TBP binding and transcription activity. J. Biol. Chem. 276,15886 -15892.[Abstract/Free Full Text]

Strahl, B. D. and Allis, C. D. (2000). The language of covalent modification. Nature 403, 41-45.[Medline]

Sypes, M. A. and Gilmour, D. S. (1994). Protein-DNA crosslinking of TFIID complexes reveals novel interactions downstream of the transcription start. Nucl. Acids Res. 22,807 -814.[Abstract]

Talavera, A. and Basilico, C. (1977). Temperature sensitive mutants of BHK cells affected in cell cycle progression. J. Cell. Physiol. 92,425 -436.[Medline]

Tsukihashi, Y., Miyake, T., Kawaichi, M. and Kokubo, T. (2000). Impaired core promoter recognition caused by novel yeast TAF145 mutations can be restored by creating a canonical TATA element within the promoter region of the TUB2 gene. Mol. Cell. Biol. 20,2385 -2399.[Abstract/Free Full Text]

Ushinsky, S. C., Bussey, H., Ahmed, A. A., Wang, Y., Friesen, J., Williams, B. A. and Storms, R. K. (1997). Histone H1 in Saccharomyces cerevisiae. Yeast 13,151 -161.[Medline]

Verrijzer, C. P., Chen, J. L., Yokomori, K. and Tjian, R. (1995). Binding of TAFs to core elements directs promoter selectivity by RNA polymerase II. Cell 81,1115 -1125.[Medline]

Vignali, M., Hassan, A. H., Neely, K. E. and Workman, J. L. (2000). ATP-dependent chromatin-remodeling complexes. Mol. Cell. Biol. 20,1899 -1910.[Free Full Text]

Walker, S. S., Reese, J. C., Apone, L. M. and Green, M. R. (1996). Transcription activation in cells lacking TAFIIs. Nature 383,185 -188.[Medline]

Walker, S. S., Shen, W.-C., Reese, J. C., Apone, L. M. and Green, M. R. (1997). Yeast TAFII145 required for transcription of G1/S cyclin genes and regulated by the cellular growth state. Cell 90,607 -614.[Medline]

Wang, E. H. and Tjian, R. (1994). Promoter-selective transcriptional defect in cell cycle mutant ts13 rescued by hTAFII250. Science 263,811 -814.[Medline]

Wang, E. H., Zou, S. and Tjian, R. (1997). TAFII250-dependent transcription of cyclin A is directed by ATF activator proteins. Genes Dev. 11,2658 -2669.[Abstract/Free Full Text]

Wassarman, D. A., Aoyagi, N., Pile, L. A. and Schlag, E. M. (2000). TAF250 is required for multiple developmental events in Drosophila. Proc. Natl. Acad. Sci. USA 97,1154 -1159.[Abstract/Free Full Text]

Weissman, J. D., Brown, J. A., Howcroft, T. K., Hwang, J., Chawla, A., Roche, P. A., Schiltz, L., Nakatani, Y. and Singer, D. S. (1998). HIV-tat binds TAFII250 and represses TAFII250-dependent transcription of major histocompatibility class I genes. Proc. Natl. Acad. Sci. USA 95,11601 -11606.[Abstract/Free Full Text]

Wieczorek, E., Brand, M., Jacq, X. and Tora, L. (1998). Function of TAF(II)-containing complex without TBP in transcription by RNA polymerase II. Nature 393,114 -115.[Medline]

Wolffe, A. P. (1998). Chromatin: Structure and Function. 3rd edn. San Diego, CA: Academic Press.

Wu, C.-H., Madabushi, L., Nishioka, H., Emanuel, P., Sypes, M., Arkhipova, I. and Gilmour, D. S. (2001). Analysis of core promoter sequences located downstream from the TATA element in the hsp70 promoter from Drosophila melanogaster. Mol. Cell. Biol. 21,1593 -1602.[Abstract/Free Full Text]