From the Unit of Molecular Morphogenesis, Laboratory
of Molecular Embryology, NICHD, National Institutes of Health,
Bethesda, Maryland 20892-5431 and the
Department of Pathology,
Emory University, Woodruff Memorial Research Building, Atlanta, Georgia
30322
Received for publication, December 14, 2000, and in revised form, January 17, 2001
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ABSTRACT |
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N-CoR (nuclear receptor corepressor) is a
corepressor for multiple transcription factors including unliganded
thyroid hormone receptors (TRs). In vitro, N-CoR can
interact with the Sin3 corepressor, which in turn binds to the histone
deacetylase Rpd3 (HDAC1), predicting the existence of a corepressor
complex containing N-CoR, Sin3, and histone deacetylase. However,
previous biochemical studies of endogenous Sin3 complexes have failed
to find an N-CoR association. Xenopus laevis eggs and
oocytes contain all of the necessary components for transcriptional
repression by unliganded TRs. In this study, we report the biochemical
fractionation of three novel macromolecular complexes containing N-CoR,
two of which possess histone deacetylase activity, from
Xenopus egg extract. One complex contains Sin3, Rpd3, and
RbAp48; the second complex contains a Sin3-independent histone
deacetylase; and the third complex lacks histone deacetylase activity.
This study describes the first biochemical isolation of endogenous
N-CoR-containing HDAC complexes and illustrates that N-CoR associates
with distinct histone deacetylases that are both dependent and
independent of Sin3. Immunoprecipitation studies show that N-CoR binds
to unliganded TR expressed in the frog oocyte, confirming that N-CoR
complexes are involved in repression by unliganded TR. These
results suggest that N-CoR targets transcriptional repression of
specific promoters through at least two distinct histone deacetylase pathways.
Transcriptional regulation by many diverse groups of transcription
factors, including nuclear hormone receptors, involves coactivator and
corepressor complexes (reviewed in Refs. 1-3). N-CoR1 and SMRT (silencing
mediator for retinoid and thyroid receptors) were initially
characterized as highly homologous corepressors for unliganded TR (4,
5). Subsequently, N-CoR was identified as a Sin3 corepressor-binding
protein (6, 7). This work suggested that N-CoR-mediated repression
occurs through Sin3 recruitment of the Sin3-associated histone
deacetylase Rpd3 (HDAC1), though an endogenous Sin3-containing N-CoR
complex has never been described to date. However, recent work provides
evidence that N-CoR can associate directly with HDAC4, HDAC5, and
HDAC3, whereas SMRT can form a complex with HDAC5 and HDAC7, or with
HDAC3 (8-12). These data suggest that multiple N-CoR-containing
histone deacetylase complexes may exist to mediate transcriptional
repression. We have previously demonstrated that the frog oocyte is
capable of mediating both transcriptional activation by liganded TR and
transcriptional repression by unliganded TR, indicating that the oocyte
contains the necessary coactivator and corepressor complexes for TR
(13-15). To characterize the corepressor complexes present in eggs and oocytes, we biochemically fractionated Xenopus egg extract
and purified three distinct complexes. Our data also suggest that one
or more of the N-CoR complexes participate in the repression by
unliganded TR.
Chromatography--
Eggs were collected from mature female
Xenopus laevis, and the high-speed egg extract was prepared
exactly as described (16). All chromatography was carried out at
4 °C in Buffer A (20 mM HEPES, pH 7.6, 1.5 mM MgCl2, 1 mM EGTA, 10% glycerol,
10 mM Coimmunoprecipitations and Antibodies--
Either fractionated
egg extract (100 µl fraction) or injected oocytes (40 oocytes/sample)
were used as the protein sources. Antisera were conjugated to protein
A-Sepharose (Amersham Pharmacia Biotech) with dimethyl
pimelimidate (DMP) exactly as described (17). Coimmunoprecipitations
were carried out in Buffer A (100 mM NaCl + 0.05% Nonidet
P-40) at 4 °C for 60 min followed by a series of five washes in
Buffer A (150 mM NaCl + 0.05% Nonidet P-40). Proteins were
eluted with 100 mM glycine, pH 2.3, or used in the histone
deacetylase assay described below. All coimmunoprecipitations were
repeated at least three times. Rabbit polyclonal antibodies specific
for Xenopus N-CoR were raised against a bacterially
expressed N-terminal polypeptide (amino acids 34-272) derived from
Xenopus N-CoR
cDNA.2 Rabbit polyclonal
antibodies raised against Xenopus TR Histone Deacetylase Assay--
Histone deacetylase assays were
performed as described (16). Chicken erythrocyte core histones
enzymatically acetylated ([3H]acetyl-CoA) with
recombinant yeast Hat1p were used as the substrate (20). Reactions were
carried using 25 µl of each fraction in 25 mM Tris, pH
8.0, 50 mM NaCl, 1 mM EDTA, 10% glycerol, and
2 µg of acetylated histones (400-µl final volume). The
reactions were incubated at 30 °C for 60 min and terminated with 100 µl of stop solution (0.1 N HCl and 0.16 N acetic acid). Released acetate was extracted with ethyl acetate (800 µl), and 75% of the
organic phase was counted by liquid scintillation. Experiments were
repeated at least three times.
Microinjection of Oocytes--
Oocyte preparation and
microinjections were carried out as described (18). Oocytes were
injected with 3 ng in vitro transcribed capped RNA (Ambion
Inc.) encoding Xenopus TR We used X. laevis high speed egg extracts as the source
for soluble endogenous proteins to biochemically purify endogenous complexes containing the N-CoR transcriptional corepressor. The extract
was initially fractionated over BioRex70 resin, which bound over 90%
of the Sin3 corepressor protein present in eggs (data not shown).
Surprisingly, all of the detectable N-CoR was contained in the
flow-through fraction (data not shown). Size fractionation (Sephacryl
S-300) of the BioRex70 flow-through pool demonstrated that all of the
N-CoR existed in large complexes (>669 kDa) with no detectable free
N-CoR (270 kDa, Fig. 1A).
Further fractionation of the BioRex70 flow-through protein pool over
DEAE-Sepharose separated the N-CoR into two distinct pools. Roughly
50% of the N-CoR bound to the DEAE (complex 1) and 50% remained in
the flow-through fraction (Fig. 1B). Fractionation of the
DEAE flow-through pool over SP-Sepharose again separated the N-CoR into
a bound pool (complex 2) and a flow-through pool (complex 3, Fig.
1B). Extensive purification of all three of the N-CoR
protein pools was achieved through a series of ion exchange and gel
filtration chromatographic steps as outlined in Fig. 1D.
Size fractionation of the purified complexes through Superose 6 showed
that all three N-CoR complexes continued to migrate in the MDa range
(data not shown), supporting the observation that the three N-CoR
protein pools are in fact distinct macromolecular complexes and not
dissociation products. A summary of a typical purification is presented
in Table I.
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
MATERIALS AND METHODS
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
-glycerophosphate, 0.5 mM
dithiothreitol, 1 mM phenylmethylsulfonyl fluoride, 2 µg/ml pepstatin A, 1 µg/ml aprotinin, and 1 µg/ml leupeptin). Egg
extract was initially fractionated using BioRex70 resin (Bio-Rad) in
Buffer A. The flow-through fraction was fractionated over
DEAE-Sepharose (Amersham Pharmacia Biotech) with a step elution in
Buffer A (to 350 mM NaCl). The DEAE (in 350 mM
NaCl) step was further fractionated by linear salt gradient elution
from Mono Q HR10/10 (Amersham Pharmacia Biotech). The peak N-CoR
fractions were pooled and loaded directly onto a 110-ml Superose 6 (Amersham Pharmacia Biotech) gel filtration column in Buffer A (in 150 mM NaCl) with 0.04% Triton X-100. The peak N-CoR fractions
were fractionated by linear salt gradient elution from Mono S HR5/5.
The DEAE flow-through pool was fractionated on SP-Sepharose (Amersham
Pharmacia Biotech) with a step elution in Buffer A (to 350 mM NaCl). The SP (350 mM) pool was fractionated
using a linear salt gradient elution from a Mono Q HR5/5 (Amersham
Pharmacia Biotech) column followed by gel filtration through Superose 6 as above. The SP-Sepharose flow-through fraction was fractionated over
Mono Q 10/10 followed by gel filtration as above. The peak N-CoR
fractions were further fractionated over Mono Q 5/5 as above.
, Sin3, Rpd3, and
RbAp48 have been described (13, 34). HDAC5 antibody was a generous gift
from S. Khochbin (19). HDAC3 antibodies were purchased from Santa
Cruz Biotechnology (Santa Cruz, CA).
and or RXR
. Injected oocytes
were incubated for 16 h at 18 °C with or without thyroid hormone (50 nM T3) prior to homogenization in
Buffer A (100 mM NaCl).
RESULTS
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Fig. 1.
Biochemical fractionation of
Xenopus egg extract reveals three distinct N-CoR
complexes. A, all of the N-CoR in Xenopus
egg extracts exists in high molecular weight complexes as determined by
sizing fractionation of the BioRex70 flow-through fraction through
Sephacryl S-300 resin. Selected fractions from resin were analyzed on
Western blot using anti-Xenopus N-CoR antibody.
B, Western blot analysis with anti-Xenopus N-CoR
antibody on initial steps of fractionation indicate that
Xenopus N-CoR exists in three complexes that can be
distinguished by ion exchange chromatography over DEAE and
SP-Sepharose. C, DEAE step fractionation of the BioRex70
flow-through separates N-CoR into Sin3-dependent (elution)
and Sin3-independent (flow-through) fractions. Western blot analysis on
the DEAE step fractionation, using antibodies against the proteins
indicated on the right, shows the partitioning of
Sin3/Rpd3-containing fractions. D, flow chart of the N-CoR
purification scheme summarizes the chromatographic procedures described
in the text.
Protein recovery data for the purification of N-CoR complexes
The polypeptide profiles of the three N-CoR complexes were determined
by silver-staining SDS-PAGE separations of the final step of
fractionation. These results showed that each complex was largely pure
and consisted of multiple distinct polypeptides (Fig.
2). Complex 1 contains eight
polypeptides, whereas complex 2 and complex 3 each contain four
polypeptides. Because N-CoR can interact with Sin3, and Sin3 can
interact with Rpd3, we assayed the presence of the Sin3 and Rpd3
proteins as well as histone deacetylase activity in the three N-CoR
complexes. Western blot analyses of the final steps of the
purifications identified complex 1 as containing Sin3 (p150) and Rpd3
(p58) whereas neither complex 2 nor complex 3 contained either Sin3 or
Rpd3 (Fig. 2, B and C). Interestingly, histone
deacetylase activity was found to precisely cofractionate with the
N-CoR protein for both complexes 1 and 2 (Fig.
3, A and B). These
data indicate that complex 2 possesses a Sin3-independent histone
deacetylase. Complex 3 contained no detectable histone deacetylase
activity (Fig. 3C). Because N-CoR complexes 1 and 2 each
contained histone deacetylase activity, we tested for the presence of
RbAp48, a protein that binds to the retinoblastoma A tumor suppressor
and has been found in several histone deacetylase complexes (Refs.
21-25). We found that RbAp48 was present in complex 1 but absent in
complexes 2 and 3 (Fig. 2). Thus, complex 1 contains the predicted
N-CoR complex components, mainly N-CoR, Rpd3, Sin3, and RbAp48, whereas
complexes 2 and 3 are novel and do not appear to share any subunits
with complex 1.
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To confirm the physical associations between N-CoR and the known
components of the complexes, we performed coimmunoprecipitation experiments (Fig. 4). Immunoprecipitation
reactions were carried out using antiserum against N-CoR, Sin3, or Rpd3
as the precipitating antibodies. Xenopus egg extract
fractionated through the DEAE step, which separates complex 1 from
complexes 2 and 3 (Fig. 1B), was used as the protein source.
The precipitation products were assayed by either Western blot analysis
using the N-CoR antibody (Fig. 4A) or by histone deacetylase
assay (Fig. 4B). Reactions using either the Sin3, N-CoR, or
Rpd3 antibodies as the precipitating antibody all immunoprecipitated
N-CoR protein when the DEAE-0.35 M step elution (containing
complex 1; Fig. 4A, top panel) was used as the protein
source (Fig. 4A, lanes 2-4). However, when the DEAE
flow-through fraction (containing complexes 2 and 3; Fig. 4A,
lower panel) was used as the protein source, only the N-CoR
antibody immunoprecipitated N-CoR protein, whereas the Sin3 and Rpd3
antibodies failed to immunoprecipitate any detectable N-CoR protein
(Fig. 4A, lanes 7-8). These data confirm the
association of N-CoR with Sin3 and Rpd3 in complex 1 as well as the
lack of association between N-CoR and Sin3 or Rpd3 in complexes 2 and 3. For both the DEAE elution and flow-through fractions, an irrelevant antibody (Irr) failed to immunoprecipitate N-CoR protein (Fig. 4A, lanes 5 and 10). In addition,
antibodies against N-CoR specifically immunoprecipitated histone
deacetylase activity from both protein pools (Fig. 4B).
These data support the existence of at least two independent
multisubunit N-CoR/histone deacetylase complexes. In addition, these
results show a physical association of N-CoR with Sin3, Rpd3, and HDAC
activity in complex 1 (but not in complexes 2 or 3) and N-CoR with HDAC
activity in complex 2.
|
We have shown previously that unliganded TR represses target
promoters in frog oocytes and that this repression can be reversed by
blocking HDAC activity (15). To investigate if any of the N-CoR
complexes participate in this repression, we overexpressed TR
and
its heterodimer partner RXR
(9-cis retinoic acid receptor) by
microinjecting in vitro transcribed mRNA into frog
oocytes and analyzing associations with N-CoR. Immunoprecipitation
experiments using antibodies against TR
(Fig.
5A) indicate that TR
/RXR
heterodimers (lanes 2 and 3), as well as TR
homodimers (lanes 4 and 5) interact with
endogenous N-CoR in a thyroid hormone
(T3)-dependent manner. Immunoprecipitation
experiments using precipitating antibodies against N-CoR (Fig.
5B) confirm a ligand-dependent interaction between N-CoR and TR
(lanes 2-5).
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DISCUSSION |
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N-CoR was initially characterized as a corepressor for unliganded TRs; however, it has been shown to participate in transcriptional repression through other transcription factors (reviewed in Refs. 2 and 26). Mice lacking N-CoR have multiple developmental defects and show that N-CoR is required for the repressive effects of several classes of DNA-binding transcriptional repressors (27). How N-CoR is differentially targeted to these transcription factors in vivo is unknown. N-CoR-mediated repression has been shown to involve the mSin3 corepressor and histone deacetylase activities (6, 7). However, mSin3 complexes containing N-CoR have so far eluded biochemical purification (28-30). We have purified two N-CoR/histone deacetylase complexes from Xenopus eggs and one N-CoR complex of unknown biological activity. All three N-CoR complexes are very large in size (>MDa) and consist of multiple polypeptides.
Two of the N-CoR complexes clearly have histone deacetylase activity (Fig. 3, A and B); however, the absence of Rpd3 (HDAC1) in N-CoR complex 2 suggested the presence of alternative histone deacetylases. Currently, seven histone deacetylases have been found in mammals that are separated into two different classes based on amino acid homology; class I contains Rpd3 (HDAC1), HDAC2, and HDAC3 whereas class II contains HDAC4-7 (9, 18, 31-33). Data from other systems indicate that N-CoR interacts with multiple HDACs including both class I and class II (8, 11, 12). These HDAC proteins are generally well conserved during evolution, making it feasible to use heterologous antibodies to check for the presence of various HDACs in the frog complexes despite the lack of sequence information on frog HDAC2-7. We obtained antibodies raised against mammalian HDAC3, 4, and 5 for Western blot analysis of the purified complexes. Only antibodies against HDAC3 and HDAC5 detected polypeptides of similar size as their mammalian homologs (Fig. 1C). However, Western blot analysis of the purified complexes with the HDAC3 and HDAC5 antibodies indicated that neither HDAC3 nor HDAC5 was present in any of the complexes (data not shown). Thus, whereas complex 1 contains Rpd3 (HDAC1), complex 2 clearly does not contain Rpd3 (HDAC1, Fig. 2B). However, we cannot rule out or identify any of the other HDACs with the available reagents.
In addition to having distinct polypeptide compositions, visualization by silver staining (assuming equivalent staining sensitivities among all of the various polypeptides) revealed that the three N-CoR complexes do not appear to have a 1:1 stoichiometry among all of the associated polypeptides in relation to N-CoR (Fig. 2). In complex 1, six of the eight polypeptides appear to be in a 1:1 ratio with N-CoR, whereas Rpd3 (2:1) and RbAp48 (4:1) are clearly more abundant. The resulting mass of complex 1 is predicted to be slightly more than 1 MDa. The multiple copies of Rpd3 and RbAp48 in the complex may suggest their functions as the catalytic subunit and a histone-interacting subunit, respectively. The four subunits of complex 2 (N-CoR, p115, p60, and p52), appear to have a stoichiometry of 1:1:2:4 respectively. It is possible that the complex exists as a multimer in vivo as the mass of the complex is greater than 1 MDa when assayed by gel filtration chromatography even though the sum of the polypeptides is only 700 kDa. Complex 3 also consists of four polypeptides (N-CoR, p120, p65, and p29), with a stoichiometry of 2:3:1:1, respectively, predicting a mass of 1 MDa. The role of the multiple subunits may indicate that the complexes must interact with multiple targeting proteins or additional corepressor complexes in vivo. Clearly, further studies on the exact stoichiometry of these complexes and their biochemical and molecular properties are required to determine their biological functions and mechanisms.
The ability of unliganded TRs to repress gene transcription in the frog
oocyte in a histone deacetylase-dependent manner together with our isolation of two N-CoR-containing histone deacetylase complexes argues that one or more of these complexes participates in
the repression process. This conclusion is supported by the interaction
of overexpressed TR with N-CoR in the frog oocytes, where all of the
N-CoR is present in large complexes. Whereas the functional differences
among these complexes remain to be investigated, our findings provide
an explanation for some inconsistent earlier observations. First, N-CoR
was initially shown to interact with Rpd3 (HDAC1) through mSin3, but
N-CoR/mSin3/Rpd3 complexes have eluded biochemical purification
in vivo. Second, N-CoR has been shown to be able to interact
with both class I and class II histone deacetylases in vitro
and form complexes with them in vivo (8, 9, 11, 12). The
nature of such complexes is yet unknown; however, all are independent
of mSin3A. Our results here demonstrate that these possibilities
coexist in vivo. The failure of other studies to detect the
multiple complexes is likely because of the choice of the systems and
the purification procedures, which we found to be crucial for the
separation and isolation of the three complexes. It is also worth
noting that our procedure allowed us to successfully purify the first
complex that contains Sin3, Rpd3 (HDAC1), and RbAp48 together.
Extensive studies including coimmunoprecipitations have demonstrated
pairwise associations between mSin3A, Rpd3 (HDAC1), and RbAp48,
suggesting that the three proteins may exist together in a complex.
However, until our study here, such a complex had eluded purification.
Our data here provide a potential mechanism whereby N-CoR complexes are
differentially recruited by specific transcriptional regulators to
repress target genes. An additional level of regulation may come from
changes in the ratio among the various N-CoR complexes or from
alterations in subunit concentrations. These findings provide an
opportunity to investigate these possible mechanisms in the near future.
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FOOTNOTES |
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* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
§ These authors contributed equally to this work.
¶ Present address: Laboratoire de Physiologie, MNHN, UMR CNRS 8572, 7 rue Cuvier, 75231 PARIS cedex 05, France.
** To whom correspondence should be addressed: UMM, LME, NICHD, National Institutes of Health, Bldg. 18T, Rm. 106, Bethesda, MD 20892-5431. Tel.: 301-402-1004; Fax: 301-402-1323; E-mail: Shi@helix.nih.gov.
Published, JBC Papers in Press, January 19, 2001, DOI 10.1074/jbc.C000879200
2 L. M. Sachs, P. L. Jones, N. Rouse, and Y-B. Shi, manuscript in preparation.
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ABBREVIATIONS |
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The abbreviations used are: N-CoR, nuclear receptor corepressor; HDAC, histone deacetylase; T3, triiodothyronine; TR, thyroid hormone receptor.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1. | Imhof, A., and Wolffe, A. P. (1998) Curr. Biol. 8, R422-424[Medline] [Order article via Infotrieve] |
2. |
Collingwood, T. N.,
Urnov, F. D.,
and Wolffe, A. P.
(1999)
J. Mol. Endocrinol.
23,
255-275 |
3. | Hu, I., and Lazar, M. A. (2000) Trends Endocrinol. Metab. 11, 6-10[CrossRef][Medline] [Order article via Infotrieve] |
4. | Horlein, A. J., Naar, A. M., Heinzel, T., Torchia, J., Gloss, B., Kurokawa, R., Ryan, A., Kamei, Y., Soderstrom, M., Glass, C. K., and Rosenfeld, M. G. (1995) Nature 377, 397-404[CrossRef][Medline] [Order article via Infotrieve] |
5. | Chen, J. D., and Evans, R. M. (1995) Nature 377, 454-457[CrossRef][Medline] [Order article via Infotrieve] |
6. | Alland, L., Muhle, R., Hou, H., Jr., Potes, J., Chin, L., Schreiber-Agus, N., and DePinho, R. A. (1997) Nature 387, 49-55[CrossRef][Medline] [Order article via Infotrieve] |
7. | Heinzel, T., Lavinsky, R. M., Mullen, T. M., Soderstrom, M., Laherty, C. D., Torchia, J., Yang, W. M., Brard, G., Ngo, S. D., Davie, J. R., Seto, E., Eisenman, R. N., Rose, D. W., Glass, C. K., and Rosenfeld, M. G. (1997) Nature 387, 43-48[CrossRef][Medline] [Order article via Infotrieve] |
8. |
Wen, Y. D.,
Perissi, V.,
Staszewski, L. M.,
Yang, W. M.,
Krones, A.,
Glass, C. K.,
Rosenfeld, M. G.,
and Seto, E.
(2000)
Proc. Natl. Acad. Sci. U. S. A.
97,
7202-7207 |
9. |
Kao, H. Y.,
Downes, M.,
Ordentlich, P.,
and Evans, R. M.
(2000)
Genes Dev.
14,
55-66 |
10. |
Guenther, M. G.,
Lane, W. S.,
Fischle, W.,
Verdin, E.,
Lazar, M. A.,
and Shiekhattar, R.
(2000)
Genes Dev.
14,
1048-1057 |
11. |
Huang, E. Y.,
Zhang, J.,
Miska, E. A.,
Guenther, M. G.,
Kouzarides, T.,
and Lazar, M. A.
(2000)
Genes Dev.
14,
45-54 |
12. |
Li, J.,
Wang, J.,
Nawaz, Z.,
Liu, J. M.,
Qin, J.,
and Wong, J.
(2000)
EMBO J.
19,
4342-4350 |
13. | Wong, J., Shi, Y. B., and Wolffe, A. P. (1995) Genes Dev. 9, 2696-2711[Abstract] |
14. |
Wong, J.,
Shi, Y. B.,
and Wolffe, A. P.
(1997)
EMBO J.
16,
3158-3171 |
15. |
Wong, J.,
Patterton, D.,
Imhof, A.,
Guschin, D.,
Shi, Y. B.,
and Wolffe, A. P.
(1998)
EMBO J.
17,
520-534 |
16. | Wade, P. A., Jones, P. L., Vermaak, D., and Wolffe, A. P. (1998) Methods Enzymol. |
17. | Harlow, E., and Lane, D. (1999) Using Antibodies: a Laboratory Manual , pp. 321-325, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y |
18. |
Fischle, W.,
Emiliani, S.,
Hendzel, M. J.,
Nagase, T.,
Nomura, N.,
Voelter, W.,
and Verdin, E.
(1999)
J. Biol. Chem.
274,
11713-11720 |
19. |
Lemercier, C.,
Verdel, A.,
Galloo, B.,
Curtet, S.,
Brocard, M. P.,
and Khochbin, S.
(2000)
J. Biol. Chem.
275,
15594-15599 |
20. | Parthun, M. R., Widom, J., and Gottschling, D. E. (1996) Cell 87, 85-94[Medline] [Order article via Infotrieve] |
21. | Qian, Y. W., Wang, Y. C., Hollingsworth, R. E., Jr., Jones, D., Ling, N., and Lee, E. Y. (1993) Nature 364, 648-652[CrossRef][Medline] [Order article via Infotrieve] |
22. |
Nicolas, E.,
Morales, V.,
Magnaghi-Jaulin, L.,
Harel-Bellan, A.,
Richard-Foy, H.,
and Trouche, D.
(2000)
J. Biol. Chem.
275,
9797-9804 |
23. | Wade, P. A., Jones, P. L., Vermaak, D., and Wolffe, A. P. (1998) Curr. Biol. 8, 843-846[Medline] [Order article via Infotrieve] |
24. | Zhang, Y., LeRoy, G., Seelig, H. P., Lane, W. S., and Reinberg, D. (1998) Cell 95, 279-289[Medline] [Order article via Infotrieve] |
25. | Zhang, Y., Iratni, R., Erdjument-Bromage, H., Tempst, P., and Reinberg, D. (1997) Cell 89, 357-364[Medline] [Order article via Infotrieve] |
26. |
Glass, C. K.,
and Rosenfeld, M. G.
(2000)
Genes Dev.
14,
121-141 |
27. | Jepsen, K., Hermanson, O., Onami, T. M., Gleiberman, A. S., Lunyak, V., McEvilly, R. J., Kurokawa, R., Kumar, V., Liu, F., Seto, E., Hedrick, S. M., Mandel, G., Glass, C. K., Rose, D. W., and Rosenfeld, M. G. (2000) Cell 102, 753-763[Medline] [Order article via Infotrieve] |
28. | Hassig, C. A., Fleischer, T. C., Billin, A. N., Schreiber, S. L., and Ayer, D. E. (1997) Cell 89, 341-347[Medline] [Order article via Infotrieve] |
29. | Laherty, C. D., Billin, A. N., Lavinsky, R. M., Yochum, G. S., Bush, A. C., Sun, J. M., Mullen, T. M., Davie, J. R., Rose, D. W., Glass, C. K., Rosenfeld, M. G., Ayer, D. E., and Eisenman, R. N. (1998) Mol. Cell 2, 33-42[Medline] [Order article via Infotrieve] |
30. | Jones, P. L., Veenstra, G. J., Wade, P. A., Vermaak, D., Kass, S. U., Landsberger, N., Strouboulis, J., and Wolffe, A. P. (1998) Nat. Genet. 19, 187-191[CrossRef][Medline] [Order article via Infotrieve] |
31. |
Rundlett, S. E.,
Carmen, A. A.,
Kobayashi, R.,
Bavykin, S.,
Turner, B. M.,
and Grunstein, M.
(1996)
Proc. Natl. Acad. Sci. U. S. A.
93,
14503-14508 |
32. |
Yang, W. M.,
Yao, Y. L.,
Sun, J. M.,
Davie, J. R.,
and Seto, E.
(1997)
J. Biol. Chem.
272,
28001-28007 |
33. |
Grozinger, C. M.,
Hassig, C. A.,
and Schreiber, S. L.
(1999)
Proc. Natl. Acad. Sci. U. S. A.
96,
4868-4873 |
34. |
Vermaak, D.,
Wade, P. A.,
Jones, P. L.,
Shi, Y.-B.,
and Wolffe, A. P.
(1999)
Mol. Cell. Biol.
19,
5847-5860 |