p62, A TFIIH Subunit, Directly Interacts with Thyroid Hormone Receptor and Enhances T3-Mediated Transcription

Ying Liu1, Shinichiro Ando1, Xianmin Xia, Refeng Yao, Myung Kim, Joseph Fondell and Paul M. Yen

Department of Medicine (X.X., P.M.Y.), Johns Hopkins Bayview Medical Center, Johns Hopkins University, Baltimore, Maryland 21224; Molecular Regulation and Neuroendocrinology Section (Y.L., S.A., R.Y.), Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases and National Heart, Lung, and Blood Institute (M.K.), National Institutes of Health, Bethesda, Maryland 20892; and Department of Physiology and Biophysics (J.F.), University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854

Address all correspondence and requests for reprints to: Paul M. Yen, M.D., Endocrinology Division, Department of Medicine, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, Room B114, Baltimore, Maryland 21224. E-mail: pyen3{at}jhmi.edu.


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 RESULTS
 DISCUSSION
 MATERIALS AND METHODS
 REFERENCES
 
Currently, little is known about the direct interactions of general transcription factors and nuclear hormone receptors. To investigate the potential role of the general transcription factor, TFIIH, in T3-mediated transcriptional activation, we examined thyroid hormone receptor (TR) interaction with individual TFIIH subunits in a yeast-two hybrid system. Among the nine subunits of TFIIH studied, only p62 subunit interacted with TRß in a ligand-dependent manner. Glutathione-S-transferase pull-down and in vivo coimmunoprecipitation studies also demonstrated direct TR/p62 interaction. Using chromatin immunoprecipitation assays, we showed that TFIIH subunits were corecruited on or near an endogenous thyroid hormone response element upon T3 addition. Cotransfection studies with TSA201 cells showed that p62 increased T3-mediated transcription, which could be further enhanced when p62 and another TFIIH subunit, p44, were cotransfected simultaneously. Taken together, these data suggest that TRs can interact directly with a subunit of TFIIH and may provide an alternative pathway for nuclear receptor communication with the general transcription machinery that circumvents coactivators.


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 RESULTS
 DISCUSSION
 MATERIALS AND METHODS
 REFERENCES
 
THYROID HORMONE RECEPTORS (TRs) are nuclear hormone receptors that are ligand-regulatable transcription factors (1, 2). There are two major TR isoforms, TR{alpha} and TRß, encoded on separate genes. TRs bind to thyroid hormone response elements (TREs) in the promoters of target genes and regulate their transcription. Unliganded TRs bind to corepressors such as nuclear receptor corepressor or silencing mediator for retinoic and TRs, and repress basal transcription by recruiting histone deacetylases, and changing local chromatin structure (1, 2, 3). In the presence of T3, corepressor complexes are released from TRs, and liganded TRs associate with coactivator complexes such as steroid receptor coactivator (SRCs) and histone acetyl transferases such as p/CAF [p300/CREB (cAMP response element binding protein)-binding protein-associated factor], and vitamin D receptor-interacting protein/TR-associated proteins (DRIP/TRAPs), leading to increased local histone acetylation, recruitment of general transcription factors and RNA polymerase II and increased transcriptional activation (4, 5, 6, 7). Recent chromatin immunoprecipitation (ChIP) studies have suggested that liganded TRs and estrogen receptors (ERs) recruit coactivators in a temporal, and perhaps cyclical, pattern (8, 9, 10, 11).

TFIIH is a multisubunit complex that plays important roles in both transcription and DNA repair (12, 13). Mutations in several individual subunits have been implicated in human genetic disorders such as xeroderma pigmentosa and Cockayne’s disease (12, 13). Recently, several subunits of TFIIH have been shown to interact with nuclear hormone receptors and promote transcriptional activation. In particular, cyclin-dependent kinase (cdk) 7 is associated with the ER and promotes its phosphorylation at serine 118 (14). TFIIH subunits also may be associated with androgen and retinoic acid receptors (15, 16). To investigate the potential role of TFIIH in T3-mediated transcriptional activation, we examined TR interaction with individual TFIIH subunits in a yeast-two hybrid system. We identified p62 as the only subunit that interacted directly with TRß in a ligand-dependent-manner. We then demonstrated that p62 alone or in combination with another associated TFIIH subunit, p44, augmented T3-dependent transcriptional activation. Additionally, we showed that TFIIH subunits were recruited to the TRE of an endogenous target gene upon T3 addition. These findings suggest the potential existence of an additional mechanism for TR-mediated transcription that circumvents interaction with coactivators and thus provides new insight into the complexity of hormonal regulation of nuclear hormone receptor-mediated transcription.


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 RESULTS
 DISCUSSION
 MATERIALS AND METHODS
 REFERENCES
 
TFIIH Subunit p62 Interacts with TR in Vivo and in Vitro
We used a yeast-two hybrid system to investigate interactions between the TR and individual TFIIH subunits. Among the nine subunits of TFIIH studied, we found that TRß interacted only with the TFIIH core subunit, p62, in a ligand-dependent manner (Table 1Go). Vitamin D receptor and retinoid X acid receptor (RXR) also behaved similarly (Table 1Go and data not shown). We then examined p62 interaction with the other TFIIH subunits and found that it interacted with the core subunit, p44 (data not shown). Glutathione-S-transferase (GST) pull-down studies confirmed that TRß and RXRß interacted with p62 in a ligand-dependent manner in vitro (Fig. 1Go).


View this table:
[in this window]
[in a new window]
 
Table 1. TFIIH Subunit Interaction with TRß and RXR{alpha} (Yeast Two-Hybrid Assay)

 


View larger version (20K):
[in this window]
[in a new window]
 
Fig. 1. p62 Interacts with TRß and RXRß LBD in Vitro

p62 Was labeled with [35S]-methionine by in vitro translation. GST pull-down assays of labeled p62 were performed using GST, GST-TRßLBD and GST-RXRßLBD in the presence or absence of 1 µM of T3 or 100 nM of 9-cis-retinoic acid as described in Materials and Methods. The input lane shows 10% of the total input labeled p62. The amount of GST protein used in each assay was normalized.

 
We next examined the interaction of endogenous TRß and p62 in GH3 rat pituitary cell line by performing coimmunoprecipitation with anti-TRß antibody and Western blotting with anti-p62 antibody (Fig. 2AGo) and the reciprocal study with coimmunoprecipitation with anti-p62 antibody and Western blotting with anti-TRß antibody (Fig. 2BGo). TRß and p62 coimmunoprecipitated together in a ligand-dependent manner (+T3 > –T3), demonstrating their direct interaction in vivo.



View larger version (47K):
[in this window]
[in a new window]
 
Fig. 2. p62 and TFIIH Interactions with TRß

A, Endogenous p62 and TRß interaction in coimmunoprecipitation assay. GH3 cellular extracts were harvested at 0, 30, 60, and 120 min, and prepared as described in Materials and Methods before immunoprecipitation with anti-TRß antibody and then Western blotting with anti-p62 antibody. Lysate refers to extract that was Western-blotted with anti-p62 only (no immunoprecipitation by anti-TRß antibody). B, Reciprocal coimmunoprecipitation to show endogenous p62 and TRß interaction. GH3 cellular extracts were harvested at 0 and 30 min before immunoprecipitation with anti-p62 antibody or nonimmune rabbit IgG, and then Western blotting with anti-TRß antibody.

 
TFIIH Subunits Are Corecruited to TREs by ChIP Assays
To determine whether TRß could recruit the TFIIH complex, in addition to p62, we performed a ChIP assay of p62, p44, and cdk7 subunits on the TRE of the target gene, cholesterol 7{alpha} hydroxylase (cyp7) (Fig. 3Go). We observed recruitment of these TFIIH subunits on or near the TRE within 30 min after T3 addition, suggesting that TRß may interact rapidly with the entire TFIIH complex.



View larger version (20K):
[in this window]
[in a new window]
 
Fig. 3. TFIIH Subunit Recruitment to the cyp7 TRE by ChIP Assay after T3 Addition

Rat pituitary GH3 cells were grown for 3 d in DMEM with 10% charcoal dextran-stripped FBS, and then treated with 10–6 M T3 and harvested at 0 and 30 min. Binding of proteins to cyp7 TRE was then analyzed by ChIP assay as described in Materials and Methods. Immunoprecipitation of cross-linked DNA/protein complexes were performed with anti-p44, p62, or cdk7 antibodies, followed by purification, and PCRs with specific primer pairs that amplified the promoter region near cyp7 TRE. +T3 numbers refer to minutes after T3 addition.

 
p62 Enhances T3-Mediated Transactivation by TR
We examined the functional role of p62 on ligand-dependent transcriptional activity of TRß by cotransfecting increasing amounts of p62 expression plasmid with fixed amounts of TRß expression plasmid and a TRE-containing reporter plasmid in TSA-201 cells. As seen in Fig. 4Go, p62 enhanced T3-mediated transcription in a dose-dependent manner. Because p62 interacted with p44 in the yeast-two hybrid assay, we investigated whether these subunits may have a synergistic effect on ligand-dependent transcription by TRß in cotransfection studies (Fig. 5Go). p44 and p62 had little effect on reporter activity in the absence of TRß. When TRß was cotransfected, p44 slightly enhanced T3-dependent transcription (3- vs. 2-fold) and p62 enhanced T3-dependent transcription (5-fold). However, when both p44 and p62 were cotransfected together, they markedly enhanced T3-dependent transcription (15-fold), suggesting that their coexpression indeed had a synergistic effect. Of note, none of the other TFIIH subunits enhanced T3-mediated transcription, either alone or in combination with p62, in cotransfection studies (data not shown).



View larger version (14K):
[in this window]
[in a new window]
 
Fig. 4. p62 Enhances T3-Dependent Transcription

TRß-1 (100 ng), F2 reporter plasmid (200 ng), and ß-galactosidase control vector (50 ng), and different indicated amounts p62 expression vector, were cotransfected in TSA 201 cells (which lack endogenous TRs) in the absence or presence of 10–6 M T3 for 48 h. pcDNA vector was added to samples as needed to keep total DNA constant. Treated cells were harvested and luciferase measured as described in Materials and Methods. Luciferase activity was normalized to ß-galactosidase activity and then calculated as fold basal luciferase activity with 1-fold basal activity defined as the luciferase activity with control pcDNA vector alone in the absence of ligand. Each point represents the mean of three experiments with six to nine samples, and bars denote SD of the mean.

 


View larger version (13K):
[in this window]
[in a new window]
 
Fig. 5. p44 Synergizes with p62 to Enhance T3-Dependent Transcription

TRß-1 (100 ng), p62 expression vector (500 ng) and p44 expression vector (500 ng), F2 reporter plasmid (200 ng), and ß-galactosidase control vector (50 ng) were cotransfected in TSA 201 cells in the absence or presence of 10–6 M T3 for 48 h. pcDNA vector was added to samples as needed to keep total DNA constant. Treated cells were harvested and luciferase measured as described in Materials and Methods. Luciferase activity was normalized to ß-galactosidase activity and then calculated as fold basal luciferase activity with 1-fold basal activity defined as the luciferase activity with control pcDNA vector alone in the absence of ligand. Each point represents the mean of three experiments with six to nine samples, and bars denote SD of the mean.

 

    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 RESULTS
 DISCUSSION
 MATERIALS AND METHODS
 REFERENCES
 
We have demonstrated that a subunit of TFIIH, p62, interacts directly with TRß in a ligand-dependent manner by yeast two-hybrid, GST pull-down assays, and in vivo coimmunoprecipitation studies. Additionally, p44 and cdk7 are corecruited with p62 in a T3-dependent manner to an endogenous TRE in ChIP assays. Overexpression of p62 also increased T3-dependent transcription. It is interesting to note that cotransfection of other TFIIH subunits did not enhance T3-dependent transcription suggesting that TR/p62 interaction may be necessary for recruitment of the entire complex. These findings suggest that multiple TFIIH subunits, or perhaps the entire TFIIH complex, may be recruited to TREs during active transcription by direct interaction with liganded TRs. Moreover, given the yeast-two-hybrid and cotransfection data, such TFIIH recruitment likely requires p62 because it interacts with TR and enhances T3-mediated transcription specifically in these studies. Taken together, our data provide the strongest evidence to date implicating a TFIIH subunit in the transcriptional regulation of a nuclear hormone receptor and suggest the possibility of direct interaction of basal transcriptional machinery components with TR in T3-dependent transcription.

In further support for a critical role of TFIIH in nuclear hormone receptor transcription, cells harboring mutations in the XPD subunit of TFIIH from patients with xeroderma pigmentosum have impaired ligand-dependent transcription by several nuclear hormone receptors (17). Recently, cdk7 was shown to phosphorylate serine 118 of ER, and the phosphorylated ER had increased transcriptional activity (14). These and other findings suggest that nuclear hormone receptors may have direct or close interactions with TFIIH. Currently, little is known about TRß phosphorylation except that it may be phosphorylated in the amino terminus in response to T3 (18). It is not known whether cdk7 phosphorylates TRß in vitro or in vivo.

Although several studies have suggested that the amino-terminal activation function (AF)-1 domain of nuclear hormone receptors are important for interactions with TFIIH components (15, 16, 19), helix 12 of the carboxy-terminal ligand binding domain (LBD) appears to be critical for ligand-dependent transcriptional enhancement by TFIIH (14). In this connection, we observed that TRß, RXR{alpha}, and vitamin D receptor LBDs interacted with p62 in a ligand-dependent manner in vitro and TRß and p62 could be coimmunoprecipitated together. A recent study mapped a LXXLL motif on p62, which was critical for ER/p62 interaction (14). Of note, a mutation within the AF-2 region (helix 12) of the LBD of TRß abrogated p62 enhancement of T3-dependent transcription (Liu, Y., and P. M. Yen, unpublished results). Because helix 12 is critical for liganded nuclear hormone receptor interactions with both the SRC and DRIP/TRAP complexes, it is possible there may be a dynamic equilibrium between coactivator and general transcriptional machinery component interactions with TR. Recently, several groups have used ChIP assays to show that liganded ER and associated coactivators were recruited to estrogen response elements in a cyclical manner (8, 10, 11). In general, this recruitment correlated with histone acetylation and transcriptional activation. However, differences in the length of cycle periods for recruitment of ER and coactivators were observed by several groups (8, 10, 11). Currently, it is difficult to ascertain how much of the p62 recruitment to TREs occurs by indirect interactions with coactivators or direct interaction with TR. If the latter mechanism occurs to any significant extent, it could potentially contribute to the cyclical recruitment of coactivators observed on some hormone response elements.

Previously, unliganded TRs were shown to interact directly with TFIIB, which in turn, potentially could interfere with the assembly of preinitiation complex at the promoter (20, 21, 22). Additionally, TRß interacted with several Drosophila TATA binding protein-associated factors (TAFs), particularly TAFII 60 and TAFII 110 (23). Thus, it is possible that liganded TR interactions with TAFs may be another point of contact between receptor and general transcriptional machinery in addition to the TR/p62 interaction during T3-mediated transcription. Additionally, there are several reports of steroid hormone receptors interacting with components of the general transcriptional machinery (24, 25, 26). These findings support the notion that parallel direct contacts between nuclear hormone receptors and general transcription factors may occur, although their net contribution to ligand-mediated transcription remains to be elucidated.

Present models of nuclear hormone receptor action show that two major coactivator complexes, SRCs and DRIP/TRAPs, are involved in ligand-dependent transcription by nuclear hormone receptors (2, 5). For SRC complexes, components such as p300/CREB-binding protein-associated factor have been implicated in histone acetylation. Additionally, it is possible that acetylation of SRCs may play a role in exchanging components in the complexes (27). For DRIP/TRAP complexes, several subunits are homologous with yeast mediator proteins and likely are involved in recruitment of general transcription factors and RNA polymerase II to the minimal promoter (6, 7). It thus is assumed that coactivators and mediators are needed to facilitate protein/protein bridging between the receptor and general transcriptional machinery. In contrast, our data raise the possibility that there may be alternative, direct pathways for nuclear receptor/ general transcription factor communication. The precise contribution of these different pathways to the overall hormonal regulation of particular target genes and their interplay with each other is not known but may depend upon diverse factors such as cell context, coactivator concentration, and chromatin state of target genes.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 RESULTS
 DISCUSSION
 MATERIALS AND METHODS
 REFERENCES
 
Yeast Two-Hybrid Assay
EGY48 yeast cells, p8op-lacZ, and LexA-parental vectors (pGilda) and B42-parental vectors (pB42AD) were purchased from CLONTECH (Palo Alto, CA). Fragments of human wild-type TRß-1 ligand-binding domain (amino acid 174–461) and human RXRß ligand-binding domain (amino acid 184–462) were subcloned into EcoRI and SalI sites of pGilda to make LexA-TRßLBD and LexARXRLBD. Fragments of human p62, human p52, human p44, human p34, human xeroderma pigmentosum (XP) B, human XPD, human cdk7, human cyclinH, and human menage a trois (MAT)1 (28) gift Dr. Myung Kim, National Heart, Lung, and Blood Institute, Bethesda, MD) were subcloned into pB42AD to make B42ADp62, B42ADp52, B42ADp44, B42ADp34, B42ADXPB, B42ADXPD B42ADcdk7, B42AD cyclin H, and B42ADMAT1. LexA fusion vectors, B42AD fusion vectors, and p8op-lacZ were transformed into EGY48 according to the manufacturer’s manual. Interactions of fusion proteins were tested using selection for leucine auxotrophy and Lac Z reporter gene on plates in the presence and absence of 1 µM T3 or100 nM 9-cis RA.

GST Pull-Down Assay
p62 In pcDNA1/AMP were transcribed and translated in rabbit reticulocyte lysates (Promega, Madison, WI) with (29)methionine according to the manufacturer’s instructions. The GST fusion protein pull-down assay was performed as described previously (30). Briefly, the GST-TRß LBD and GST-RXRß LBD fusion proteins (~2 µg/lane) were bound to glutathione-Sepharose beads (Amersham Biosciences, Piscataway, NJ). The beads then were resuspended in the binding buffer [20 mM HEPES (pH 7.7), 75 mM KCl, 0.1 mM EDTA, 2.5 mM MgCl2, 0.05% Nonidet P-40, 2 mM dithiothreitol, 10% glycerol], and incubated with 5 µl of in vitro translated, [35S]-labeled p62 proteins in the presence or absence of ligands (1 µM T3, or 1 µM 9-cis-retinoic acid) for 1 h at room temperature. Beads were washed with the binding buffer in the presence or absence of the ligands, resuspended in 30 µl of 1% sodium dodecyl sulfate (SDS) sample buffer, and analyzed by SDS-PAGE and autoradiography.

Cell Culture and Transfection Assay
TSA 201 cells (a strain of HEK293 cells transformed with T antigen) were maintained in Opti-MEM (Invitrogen Life Technologies, Rockville, MD) containing 4% fetal bovine serum (FBS). After growth in Opti-MEM containing 4% dextran-treated FBS (Gemini Bio-Products, Woodland, CA) for 6 h to remove endogenous thyroid hormones, the cells were transfected by Fugene 6 Reagent (Roche Molecular Biochemicals, Indianapolis, IN) with 100 ng of F2 reporter plasmid (31), 100 ng of TRß-1 expression vector (31), various amount of p62 and p44 in pcDNAIII/Amp (Invitrogen Life Technologies). Cytomegalovirus ß-galactosidase plasmid was used as an internal control. In some samples, empty expression vector, pcDNA1/AMP, was added to equalize the total transfected plasmid concentration. Three hours after transfection, the cells were washed and incubated for 40 h with Opti-MEM containing 1% dextran-treated FBS in the absence or presence of 1 µM T3. The cells were lysed, and the cell extracts then were analyzed for both luciferase and ß-galactosidase activity to normalize for transfection efficiency.

Antibodies
Antibodies against p62 (Q-19), p44 (C-19), and CDK7 (C-4) were obtained from Santa Cruz Biotechnology (Santa Cruz, CA). Antibody against TRß-1 was obtained from Affinity BioReagents (Golden, CO).

ChIP Assay
Rat pituitary GH3 cells were grown to 90% confluence in phenol red-free DMEM supplemented with 10% dextran-treated FBS for at least 3 d. After addition of 10–6 M T3 at various time interval, ChIP assays were preformed according to manufacturer’s protocol (Upstate Biotechnology, Lake Placid, NY) with some minor modifications. Briefly, cells were cross-linked by adding formaldehyde directly to culture medium to a final concentration of 1% and incubated for 10 min at room temperature. Cells then were washed twice with ice-cold PBS and collected by scraping in 5 ml ice-cold PBS containing a protease inhibitor cocktail (Roche Molecular Biochemicals, Indianapolis, IN). Cells then were resuspended in 300-µl SDS lysis buffer containing protease inhibitor cocktail and incubated on ice for 10 min. The lysates were sonicated three times for 10 sec (Misonix, Farmingdale, NY) to reduce DNA fragment length to approximately 500–2000 bp and then subjected to centrifugation for 10 min to remove debris. Supernatants were collected and diluted 5-fold in ChIP dilution buffer containing protease inhibitor cocktail as above. Two hundred microliters of this chromatin solution were saved to quantitate the amount of input DNA present in different samples before immunoprecipitation. The rest of the chromatin solutions were precleared with 60 µl of salmon sperm DNA/protein A agarose slurry for 1 h at 4 C with agitation if antibodies were generated by rabbit. Alternatively, chromatin solutions were precleared with 60 µl of protein A/G plus agrose slurry (Santa Cruz Biotechnology) with 2 µg of sheared salmon sperm DNA if antibodies were generated from species other than rabbit. Immunoprecipitation was performed overnight with agitation at 4 C with specific antibodies. Immunoprecipitated chromatin-complexes were collected with 60 µl of salmon sperm DNA/protein A agarose slurry for 2 h at 4 C with agitation if antibodies were generated by rabbit. Immune chromatin-complexes were collected with 60 µl of Protein A/G plus agarose slurry (Santa Cruz Biotechnology) with 2 µg of sheared salmon sperm DNA if antibodies were generated from species other than rabbit. Precipitates then were washed sequentially in low-salt immune complex wash buffer, high-salt immune complex wash buffer, and LiCl immune complex wash buffer for 3–5 min. Beads then were washed two times in Tris-EDTA buffer and extracted two times with 1% SDS, 0.1 M NaHCO3. Pooled eluates as well as saved chromatin solution for quantitating the amount of input DNA from above were heated at 65 C for 4 h in 0.2 M NaCl solution to reverse the formaldehyde cross-linking. After incubation at 45 C for 1 h of 10 µM EDTA in 40 µM Tris-HCl (pH 6.5) and 20 µg of proteinase K, DNA fragments were purified with phenol:chloform:isoamylalcohol (25:24:1) and ethanol precipitation, and reconstituted in 50 µl H20. 5 µl of DNA solution was analyzed by PCR with 25–32 cycles of amplification. For detection of the immunoprecipitated TRE promoter region, primers used for PCR of rat CYP7 TRE: forward 5'-AGT TCCATACAGTTCGCGTCC-3', reverse 5'-ACAGTGGGTCTGACTAGAC-3'. This primer yields a 454-bp product with the 3' end located 66 base pairs upstream of the transcriptional start site (GenBank accession no. M59184). The putative TRE is located 38 bp upstream of the complementary sequence of the reverse primer.


    FOOTNOTES
 
First Published Online December 29, 2004

1 Y.L. and S.A. are equal contributors. Back

Abbreviations: AF, Activator function; cdk, cyclin-dependent kinase; ChIP, chromatin immunoprecipitation; CREB, cAMP response element binding protein; cyp7, cholesterol 7{alpha} hydroxylase; DRIP/TRAP, vitamin D receptor-interacting protein/TR-associated proteins; ER, estrogen receptor; FBS, fetal bovine serum; GST, glutathione-S-transferase; LBD, ligand binding domain; MAT, menage a trois; RXR, retinoid X receptor; SDS, sodium dodecyl sulfate; SRC, steroid receptor coactivator; TAF, TATA binding protein-associated factors; TR, thyroid hormone receptor; TRE, thyroid hormone response elements; XP, xeroderma pigmentosum.

Received for publication September 27, 2004. Accepted for publication December 15, 2004.


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 RESULTS
 DISCUSSION
 MATERIALS AND METHODS
 REFERENCES
 

  1. Yen PM 2001 Physiological and molecular basis of thyroid hormone action. Physiol Rev 81:1097–1142[Abstract/Free Full Text]
  2. Zhang J, Lazar MA 2000 The mechanism of action of thyroid hormones. Annu Rev Physiol 62:439–466[CrossRef][Medline]
  3. Ordentlich P, Downes M, Evans RM 2001 Corepressors and nuclear hormone receptor function. Curr Top Microbiol Immunol 254:101–116[Medline]
  4. Torchia J, Glass C, Rosenfeld MG 1998 Co-activators and co-repressors in the integration of transcriptional responses. Curr Opin Cell Biol 10:373–383[CrossRef][Medline]
  5. McKenna NJ, Lanz RB, O’Malley BW 1999 Nuclear receptor coregulators: cellular and molecular biology. Endocr Rev 20:321–344[Abstract/Free Full Text]
  6. Ito M, Roeder RG 2001 The TRAP/SMCC/mediator complex and thyroid hormone receptor function. Trends Endocrinol Metab 12:127–134[CrossRef][Medline]
  7. Rachez C, Freedman LP 2001 Mediator complexes and transcription. Curr Opin Cell Biol 13:274–280[CrossRef][Medline]
  8. Shang Y, Hu X, DiRenzo J, Lazar MA, Brown M 2000 Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell 103:843–852[CrossRef][Medline]
  9. Sharma D, Fondell JD 2002 Ordered recruitment of histone acetyltransferases and the TRAP/mediator complex to thyroid hormone-responsive promoters in vivo. Proc Natl Acad Sci USA 99:7934–7939[Abstract/Free Full Text]
  10. Burakov D, Crofts LA, Chang CP, Freedman LP 2002 Reciprocal recruitment of DRIP/mediator and p160 coactivator complexes in vivo by estrogen receptor. J Biol Chem 277:14359–14362[Abstract/Free Full Text]
  11. Reid G, Hubner MR, Metivier R, Brand H, Denger S, Manu D, Beaudouin J, Ellenberg J, Gannon F 2003 Cyclic, proteasome-mediated turnover of unliganded and liganded ER{alpha} on responsive promoters is an integral feature of estrogen signaling. Mol Cell 11:695–707[Medline]
  12. Timmers HT 2002 Linking activators and basals in transcription: it is all in one family. Mol Cell 9:697–698[CrossRef][Medline]
  13. Egly JM 2001 The 14th Datta Lecture. TFIIH: from transcription to clinic. FEBS Lett 498:124–128[CrossRef][Medline]
  14. Chen D, Riedl T, Washbrook E, Pace PE, Coombes RC, Egly JM, Ali S 2000 Activation of estrogen receptor {alpha} by S118 phosphorylation involves a ligand-dependent interaction with TFIIH and participation of CDK7. Mol Cell 6:127–137[Medline]
  15. Lee DK, Duan HO, Chang C 2000 From androgen receptor to the general transcription factor TFIIH. Identification of cdk activating kinase (CAK) as an androgen receptor NH(2)-terminal associated coactivator. J Biol Chem 275:9308–9313[Abstract/Free Full Text]
  16. Rochette-Egly C, Adam S, Rossignol M, Egly JM, Chambon P 1997 Stimulation of RAR{alpha} activation function AF-1 through binding to the general transcription factor TFIIH and phosphorylation by CDK7. Cell 90:97–107[CrossRef][Medline]
  17. Keriel A, Stary A, Sarasin A, Rochette-Egly C, Egly JM 2002 XPD mutations prevent TFIIH-dependent transactivation by nuclear receptors and phosphorylation of RAR{alpha}. Cell 109:125–135[Medline]
  18. Ting YT, Cheng SY 1997 Hormone-activated phosphorylation of human ß1 thyroid hormone nuclear receptor. Thyroid 7:463–469[Medline]
  19. Wu X, Li H, Chen JD 2001 The human homologue of the yeast DNA repair and TFIIH regulator MMS19 is an AF-1-specific coactivator of estrogen receptor. J Biol Chem 276:23962–23968[Abstract/Free Full Text]
  20. Baniahmad A, Ha I, Reinberg D, Tsai MJ, Tsai SY, O’Malley BW 1993 Interaction of human thyroid hormone receptor ß with transcription factor TFIIB may mediate target gene derepression and activation by thyroid hormone. Proc Natl Acad Sci USA 90:8832–8836[Abstract/Free Full Text]
  21. Tong GX, Tanen MR, Bagchi MK 1995 Ligand modulates the interaction of thyroid hormone receptor ß with the basal transcription machinery. J Biol Chem 270:10601–10611[Abstract/Free Full Text]
  22. Hadzic E, Desai-Yajnik V, Helmer E, Guo S, Wu S, Koudinova N, Casanova J, Raaka BM, Samuels HH 1995 A 10 amino acid sequence in the N-terminal A/B domain of thyroid hormone receptor {alpha} is essential for transcriptional activation and interaction with the general transcription factor TFIIB. Mol Cell Biol 15:4507–4517[Abstract]
  23. Petty KJ, Krimkevich YI, Thomas D 1996 A TATA binding protein-associated factor functions as a coactivator for thyroid hormone receptors. Mol Endcorinol 10:1632–1645[CrossRef]
  24. Ing NH, Beckman JM, Tsai SY, Tsai MJ, O’Malley BW 1992 Members of the steroid hormone receptor superfamily interact with TFIIB (S300-II). J Biol Chem 267:17617–17623[Abstract/Free Full Text]
  25. Jacq X, Brou C, Lutz Y, Davidson I, Chambon P, Tora L 1994 Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor. Cell 79:107–117[Medline]
  26. Sadovsky Y, Webb P, Lopez G, Baxter JD, Fitzpatrick PM, Gizang-Ginsberg E, Cavailles V, Parker MG, Kushner PJ 1995 Transcriptional activators differ in their responses to overexpression of TATA-box-binding protein. Mol Cell Biol 15:1554–1563[Abstract]
  27. Chen H, Lin RJ, Xie W, Wilpitz D, Evans RM 1999 Regulation of hormone-induced histone hyperacetylation and gene activation via acetylation of an acetylase. Cell 98:675–686[Medline]
  28. Kim MK, Nikodem VM 1999 hnRNP U inhibits carboxy-terminal domain phosphorylation by TFIIH and represses RNA polymerase II elongation. Mol Cell Biol 19:6833–6844[Abstract/Free Full Text]
  29. Kakizawa T, Miyamoto T, Kaneko A, Yajima H, Ichikawa K, Hashizume K 1997 Ligand-dependent heterodimerization of thyroid hormone receptor and retinoid X receptor. J Biol Chem 272:23799–23804[Abstract/Free Full Text]
  30. Takeshita A, Yen PM, Ikeda M, Cardona GR, Liu Y, Koibuchi N, Norwitz ER, Chin WW 1998 Thyroid hormone response elements differentially modulate the interactions of thyroid hormone receptors with two receptor binding domains in the steroid receptor coactivator-1. J Biol Chem 273:21554–21562[Abstract/Free Full Text]
  31. Yen PM, Liu Y, Sugawara A, Chin WW 1996 Vitamin D receptors (VDRs) repress basal transcription and have dominant negative activity on T3-mediated transcription. J Biol Chem 271:10910–10916[Abstract/Free Full Text]




This Article
Abstract
Full Text (PDF)
All Versions of this Article:
19/4/879    most recent
Author Manuscript (PDF)
Purchase Article
View Shopping Cart
Alert me when this article is cited
Alert me if a correction is posted
Citation Map
Services
Email this article to a friend
Similar articles in this journal
Similar articles in PubMed
Alert me to new issues of the journal
Download to citation manager
Request Copyright Permission
Google Scholar
Articles by Liu, Y.
Articles by Yen, P. M.
Articles citing this Article
PubMed
PubMed Citation
Articles by Liu, Y.
Articles by Yen, P. M.


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals