2004/06/08 by Aihua Zhang, Percy Luk Yeung, Chia‐Wei Li +6 · 26 citations
Biochemistry, Genetics and Molecular Biology · #Epigenetics and DNA Methylation #Genomics and Chromatin Dynamics #Receptor Mechanisms and Signaling
paper · doi:10.1074/jbc.m403997200
Members of the p160 nuclear receptor coactivators interact with liganded nuclear receptors to enhance transcription of target genes. Here we identify a novel family of ankyrin repeats containing cofactors (ANCOs) that interact with the p160 coactivators. ANCO-1 binds to the conserved Per-Arnt-Sim (PAS) region of the p160 coactivators. It encodes a large nuclear protein with five ankyrin repeats, and parts of its sequences have been reported as nasopharyngeal carcinoma susceptibility protein and medulloblastoma antigen. Immunofluorescence staining reveals discrete nuclear foci of ANCO-1 that are distinct from known nuclear structures. Intriguingly, ANCO-1 also colocalizes and interacts with histone deacetylases. Transient reporter gene assay shows that ANCO-1 expression inhibits ligand-dependent transactivation by both steroid and nonsteroid nuclear receptors. Taken together, we have identified a novel family of ankyrin repeats containing cofactors that may recruit histone deacetylases to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation. Members of the p160 nuclear receptor coactivators interact with liganded nuclear receptors to enhance transcription of target genes. Here we identify a novel family of ankyrin repeats containing cofactors (ANCOs) that interact with the p160 coactivators. ANCO-1 binds to the conserved Per-Arnt-Sim (PAS) region of the p160 coactivators. It encodes a large nuclear protein with five ankyrin repeats, and parts of its sequences have been reported as nasopharyngeal carcinoma susceptibility protein and medulloblastoma antigen. Immunofluorescence staining reveals discrete nuclear foci of ANCO-1 that are distinct from known nuclear structures. Intriguingly, ANCO-1 also colocalizes and interacts with histone deacetylases. Transient reporter gene assay shows that ANCO-1 expression inhibits ligand-dependent transactivation by both steroid and nonsteroid nuclear receptors. Taken together, we have identified a novel family of ankyrin repeats containing cofactors that may recruit histone deacetylases to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation. Nuclear receptors (NRs) 1The abbreviations used are: NR, nuclear receptor; SRC, steroid receptor coactivator; RAC3, receptor-associated coactivator 3; ANCO-1/2, ankyrin repeats containing cofactors-1/2; GST, glutathione S-transferase; HDAC, histone deacetylase; DBD, DNA-binding domain; LBD, ligand-binding domain; bHLH, basic-helix-loop-helix; PAS, Per-Arnt-Sim; HA, hemagglutinin; PR, progesterone receptor; CREB, cAMP-response element-binding protein; Luc, luciferase; PML, promyelocytic leukemia protein; MMTV, mouse mammary tumor virus. are DNA-binding transcription factors that control hormone-dependent gene expression in many biological processes (1Nawaz Z. Baniahmad C. Burris T.P. Stillman D.J. O'Malley B.W. Tsai M.J. Mol. Gen. Genet. 1994; 245: 724-733Crossref PubMed Scopus (33) Google Scholar, 2Mangelsdorf D.J. Thummel C. Beato M. Herrlich P. Schütz G. Umesono K. Blumberg B. Kastner P. Mark M. Chambon P. Evans R.M. Cell. 1995; 83: 835-839Abstract Full Text PDF PubMed Scopus (6088) Google Scholar). NRs contain an N-terminal activation domain (AF-1), a central DNA-binding domain (DBD), and a C-terminal ligand-binding domain (LBD) that also contains a ligand-dependent activation function (AF-2). Two classes of cofactors, known as coactivators and corepressors, mediate the activation and repression functions of NRs, respectively. Among the corepressors, silencing mediator of retinoid and thyroid hormone receptors and nuclear receptor corepressor are two highly related proteins that bind primarily to unliganded NRs (3Chen J.D. Evans R.M. Nature. 1995; 377: 454-457Crossref PubMed Scopus (1712) Google Scholar, 4Horlein A.J. Naar A.M. Heinzel T. Torchia J. Gloss B. Kurokawa R. Ryan A. Kamei Y. Soderstrom M. Glass C.K. Rosenfeld M.G. Nature. 1995; 377: 397-404Crossref PubMed Scopus (1712) Google Scholar, 5Park E.J. Schroen D.J. Yang M. Li H. Li L. Chen J.D. Proc. Natl. Acad. Sci. U. S. 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Contrary to the corepressors, the p160 NR coactivators bind to liganded NRs to mediate transcriptional activation through recruitment of histone acetyltransferases (10Leo C. Chen J.D. Gene (Amst.). 2000; 245: 1-11Crossref PubMed Scopus (440) Google Scholar). The p160 coactivators include SRC-1 (11Oñate S.A. Tsai S.Y. Tsai M.J. O'Malley B.W. Science. 1995; 270: 1354-1357Crossref PubMed Scopus (2058) Google Scholar), GRIP1/TIF2 (12Hong H. Kohli K. Trivedi A. Johnson D.L. Stallcup M.R. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 4948-4952Crossref PubMed Scopus (614) Google Scholar, 13Hong H. Kohli K. Garabedian M.J. Stallcup M.R. Mol. Cell. Biol. 1997; 17: 2735-2744Crossref PubMed Scopus (497) Google Scholar, 14Voegel J.J. Heine M.J.S. Zechel C. Chambon P. Gronemeyer H. EMBO J. 1996; 15: 3667-3675Crossref PubMed Scopus (952) Google Scholar), and RAC3/ACTR/AIB1/pCIP/TRAM-1 (15Li H. Gomes P.J. Chen J.D. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 8479-8484Crossref PubMed Scopus (504) Google Scholar, 16Torchia J. Rose D.W. Inostroza J. Kamei Y. Westin S. Glass C.K. Rosenfeld M.G. Nature. 1997; 387: 677-684Crossref PubMed Scopus (1107) Google Scholar, 17Anzick S.L. Kononen J. Walker R.L. Azorsa D.O. Tanner M.M. Guan X.Y. Sauter G. Kallioniemi O.P. Trent J.M. Meltzer P.S. Science. 1997; 277: 965-968Crossref PubMed Scopus (1432) Google Scholar, 18Chen H. Lin R.J. Schiltz R.L. Chakravarti D. Nash A. Nagy L. Privalsky M.L. Nakatani Y. Evans R.M. Cell. 1997; 90: 569-580Abstract Full Text Full Text PDF PubMed Scopus (1268) Google Scholar, 19Takeshita A. Cardona G.R. Koibuchi N. Suen C.-S. Chin W.W. J. Biol. Chem. 1997; 272: 27629-27634Abstract Full Text Full Text PDF PubMed Scopus (325) Google Scholar). These coactivators bind to the hydrophobic cleft in LBD through LXXLL motifs (20Heery D.M. Kalkhoven E. Hoare S. Parker M.G. Nature. 1997; 387: 733-736Crossref PubMed Scopus (1772) Google Scholar, 21Shiau A.K. Barstad D. Loria P.M. Cheng L. Kushner P.J. Agard D.A. Greene G.L. Cell. 1998; 95: 927-937Abstract Full Text Full Text PDF PubMed Scopus (2255) Google Scholar). These coactivators also interact with histone acetyltransferases such as CREB-binding protein/p300 and P/CAF (22Kamei Y. Xu L. Heinzel T. Torchia J. Kurokawa R. Gloss B. Lin S.C. Heyman R.A. Rose D.W. Glass C.K. Rosenfeld M.G. Cell. 1996; 85: 403-414Abstract Full Text Full Text PDF PubMed Scopus (1926) Google Scholar, 23Blanco J.C. Minucci S. Lu J. Yang X.J. Walker K.K. Chen H. Evans R.M. Nakatani Y. Ozato K. Genes Dev. 1998; 12: 1638-1651Crossref PubMed Scopus (340) Google Scholar), tethering histone acetyltransferase activity to target promoters. Genetic studies suggest that the p160 coactivators are involved in regulating hormonal responses in mice (24Xu J. Qiu Y. DeMayo F.J. Tsai S.Y. Tsai M.J. O'Malley B.W. Science. 1998; 279: 1922-1925Crossref PubMed Scopus (597) Google Scholar, 25Xu J. Liao L. Ning G. Yoshida-Komiya H. Deng C. O'Malley B.W. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 6379-6384Crossref PubMed Scopus (458) Google Scholar, 26Wang Z. Rose D.W. Hermanson O. Liu F. Herman T. Wu W. Szeto D. Gleiberman A. Krones A. Pratt K. Rosenfeld R. Glass C.K. Rosenfeld M.G. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 13549-13554Crossref PubMed Scopus (170) Google Scholar). Among the p160 coactivators, RAC3 AIB1 is clinically important because it is amplified in breast cancers (17Anzick S.L. Kononen J. Walker R.L. Azorsa D.O. Tanner M.M. Guan X.Y. Sauter G. Kallioniemi O.P. Trent J.M. Meltzer P.S. Science. 1997; 277: 965-968Crossref PubMed Scopus (1432) Google Scholar). Furthermore, RAC3 forms a stable complex with estrogen receptor α in breast cancer cells (27Tikkanen M.K. Carter D.J. Harris A.M. Le H.M. Azorsa D.O. Meltzer P.S. Murdoch F.E. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 12536-12540Crossref PubMed Scopus (38) Google Scholar), suggesting that RAC3 may play an important role in the development of breast cancer. The p160 coactivators share a common domain structure, including a highly conserved N-terminal basic-helix-loop-helix (bHLH) and Per-Arnt-Sim (PAS) domains (10Leo C. Chen J.D. Gene (Amst.). 2000; 245: 1-11Crossref PubMed Scopus (440) Google Scholar). The PAS domain is separated into A and B regions, which are conserved among many PAS family proteins (28Huang W. Sun G.-L. Li X.-S. Cao Q. Lu Y. Jang G.-S. Zahang F.-Q. Chai J.-R. Wang Z.-Y. Waxman S. Chen Z. Chen S.-J. Blood. 1993; 82: 1264-1269Crossref PubMed Google Scholar). The bHLH-PAS domain is implicated in mediating protein-protein interaction (see Refs. 34Behrends U. Schneider I. Rossler S. Frauenknecht H. Golbeck A. Lechner B. Eigenstetter G. Zobywalski C. Muller-Weihrich S. Graubner U. Schmid I. Sackerer D. Spath M. Goetz C. Prantl F. Asmuss H.P. Bise K. Mautner J. Int. J. Cancer. 2003; 106: 244-251Crossref PubMed Scopus (49) Google Scholar, 35Belandia B. Orford R.L. Hurst H.C. Parker M.G. EMBO J. 2002; 21: 4094-4103Crossref PubMed Scopus (198) Google Scholar, 36Kim J.H. Li H. Stallcup M.R. Mol. Cell. 2003; 12: 1537-1549Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar). We thought to search for new proteins that may regulate the function of RAC3 by interacting with the conserved bHLH-PAS domain. Previously, we have identified a human homologue of the yeast MMS19 as a RAC3-interacting protein, which also interacts with estrogen receptor α in a ligand-independent manner (29Wu X. Li H. Chen J.D. J. Biol. Chem. 2001; 276: 23962-23968Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar). Here, we report the identification and characterization of another RAC3-interacting protein, designated ANCO-1 for ankyrin repeats containing cofactor-1. We found that ANCO-1 and likely its related protein ANCO-2 may represent a novel class of nuclear receptor corepressors that may inhibit transcriptional activity of NRs through interfering with the coactivator function of p160 by recruiting HDACs. Plasmids and Yeast Two-hybrid Screen—The bait plasmid pGBT-RAC3 bHLH-PAS (amino acids 1–408) used in the yeast two-hybrid screen and the other RAC3 constructs are as described previously (15Li H. Gomes P.J. Chen J.D. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 8479-8484Crossref PubMed Scopus (504) Google Scholar, 30Li H. Chen J.D. J. Biol. Chem. 1998; 273: 5948-5954Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar). A yeast two-hybrid screen of the human placenta cDNA library (Clontech) was conducted in Y190 cells with ∼2 million transformants. Three RAC3-interacting cDNA clones, RS14, RS2, and RS13, were isolated, and they encode the C-terminal amino acids 2183–2663, 2279–2663, and 2369–2663 of ANCO-1, respectively. The RS2 and RS13 sequences match to a genomic clone on chromosome Xq27.1–Xq27.3; however, the RS14 N-terminal region differs from the genomic sequence. These clones were later found to match exactly to another genomic clone on chromosome 16q24.3 (RP11-781H20), and further analysis indicates that the sequence on Xq27.1 may be a pseudogene. Stepwise search and assembly of many overlapping expressed sequence tag clones in comparison with the genomic sequence predicted a full-length ANCO-1 of ∼9.1 kb. The full-length ANCO-1 vector was constructed using DNA fragments from RS13, the genomic clone PR11-781H20, and the expressed sequence tag clone tf70e12. Constructions of other plasmids were achieved by standard methods, and details are available upon requests. GST Pull-down Assay—GST fusion proteins were expressed in BL-21 cells and purified by standard glutathione agarose beads. The [35S]methionine-labeled proteins were synthesized in reticulocyte lysate (Promega). Five μg of GST fusion proteins conjugated to glutathione agarose beads were incubated with 5 μl of in vitro translated proteins at 4 °C overnight in a binding buffer as described before (31Li H. Leo C. Zhu J. Wu X. O'Neil J. Park E.J. Chen J.D. Mol. Cell. Biol. 2000; 20: 1784-1796Crossref PubMed Scopus (307) Google Scholar). Pellets were washed four times with binding buffer, and bound proteins were eluted in SDS sample buffer followed by SDS-PAGE and autoradiography. Northern Blot—Multiple tissue and cancer cells Northern blots were purchased from Clontech and probed with 32P-labeled ANCO-1 cDNA fragments using the ExpressHyb solution. The blot was washed twice for 20 min in 2× SSC/0.1% SDS at room temperature and subject to autoradiography at -70 °C. Immunofluorescence Microscopy—Cells were grown on cover glasses and then fixed with cold methanol/acetone (1:1) mixture for 2 min and processed for immunofluorescence staining as described previously (32Dyck J.A. Maul G.G. Miller Jr., W.H. Chen J.D. Kakizuka A. Evans R.M. Cell. 1994; 76: 333-343Abstract Full Text PDF PubMed Scopus (724) Google Scholar). Thirty-six hours after transfection, cells were stained with primary antibodies followed by rhodamine- or fluorescein-conjugated secondary antibodies. Cell nuclei were with and cover glasses were with The were with a and with the and The antibodies were purchased from and antibodies were from The were with antibodies. The domains and were by antibodies and human respectively. assay was conducted as described before (31Li H. Leo C. Zhu J. Wu X. O'Neil J. Park E.J. Chen J.D. Mol. Cell. Biol. 2000; 20: 1784-1796Crossref PubMed Scopus (307) Google Scholar). cells were with and and the lysate was after The and proteins were with or respectively. The agarose and antibodies were purchased from blot was conducted using from Cell and Transient were grown at °C with in with and 5 to transfection, cells were in at a of in with was using as described (31Li H. Leo C. Zhu J. Wu X. O'Neil J. Park E.J. Chen J.D. Mol. Cell. Biol. 2000; 20: 1784-1796Crossref PubMed Scopus (307) Google Scholar). cells were washed with and with containing were after for and as described previously (15Li H. Gomes P.J. Chen J.D. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 8479-8484Crossref PubMed Scopus (504) Google Scholar). of was identified from a yeast two-hybrid screen as a RAC3-interacting Three ANCO-1 cDNA clones overlapping C-terminal domains were the interaction and to the interacting on RAC3, cDNA clones were and into yeast cells with a of RAC3 in the RS13 clone amino acids 2369–2663 of ANCO-1 with the and bHLH-PAS fragments of RAC3, it interaction with the bHLH, or the domain of were with RS14 and RS2 clones The interaction of with RAC3 in vitro was then by GST assay in which bound to the and These suggest that ANCO-1 interacts and with the PAS region of ANCO-1 also interacts with full-length p160 coactivators, a GST assay was conducted using in vitro translated full-length RAC3, and We found that both and the (amino acids bound to the full-length RAC3, and SRC-1 These suggest that may interact with full-length p160 coactivators through the C-terminal amino acids of interaction was further by two-hybrid assay in cells in which the RAC3 with and a ANCO-1 (amino acids Northern blot analysis a large in many human and cancer which the full-length The expression of ANCO-1 among and cancer with the expression in and leukemia The of are in of Intriguingly, the N-terminal also two of the C-terminal an suggesting the of of of ANCO-1 and full-length ANCO-1 contains amino acids with an of The known domain in ANCO-1 is the five ankyrin repeats Sci. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). ankyrin region is to a nasopharyngeal carcinoma susceptibility protein which a on to and of expressed sequence tag sequences in other suggesting that be in the nasopharyngeal carcinoma A also a medulloblastoma sequence to amino acids of ANCO-1 contains a after U. Schneider I. Rossler S. Frauenknecht H. Golbeck A. Lechner B. Eigenstetter G. Zobywalski C. Muller-Weihrich S. Graubner U. Schmid I. Sackerer D. Spath M. Goetz C. Prantl F. Asmuss H.P. Bise K. Mautner J. Int. J. Cancer. 2003; 106: 244-251Crossref PubMed Scopus (49) Google Scholar), a to ankyrin repeats, ANCO-1 contain other analysis shows that the central region of ANCO-1 is highly and contains many nuclear Furthermore, an protein of function was found in and and We protein The ANCO-1 and ANCO-2 is at the N-terminal and C-terminal domains and ANCO-2 also interacts with p160 coactivators in GST assay suggesting that ANCO-1 and ANCO-2 may be of ANCO-1 at Nuclear and with interaction of ANCO-1 with transcriptional coactivators that ANCO-1 may be involved in gene we nuclear of ANCO-1 by immunofluorescence and cells were with expression vector and with antibodies and antibodies that known nuclear structures. Intriguingly, we found that was ANCO-1 in the it was also at discrete foci These ANCO-1 nuclear foci are distinct from other known nuclear domains such as the and ANCO-1 nuclear foci may be to transcriptional we of ANCO-1 with transcriptional we found ANCO-1 nuclear foci with and These are because ANCO-1 with the nuclear or the the of ANCO-1 with we a GST assay to ANCO-1 interacts or with HDACs. The that the domain binds to as as and The domain of ANCO-1 is from the domain because the bound p160 coactivators Furthermore, a assay also the of an protein complex in These suggest in to the p160 coactivators, ANCO-1 may also interact with HDACs. ANCO-1 by Nuclear interaction of ANCO-1 with that ANCO-1 may be a on transcriptional by we ANCO-1 in cells and its on ligand-dependent transcriptional activation by We found that ANCO-1 in a of transactivation by NRs, including for progesterone and A and ANCO-1 on the activity of the reporter ANCO-1 also on a reporter in the of or fusion protein suggesting that ANCO-1 may inhibit transcription Furthermore, ANCO-1 expression also transactivation of the reporter by in a manner These suggest that ANCO-1 may function as a for NRs by ligand-dependent transcriptional we the of p160 coactivators on transcriptional We the of transactivation by ANCO-1 with the coactivator with expression of ANCO-1 transactivation on the expression of the transactivation and of ANCO-1 the suggesting that ANCO-1 may the coactivator function of of also transcriptional repression on transactivation in a manner a fusion protein was to transcription of the reporter suggesting that ANCO-1 contains transcriptional repression Taken together, that the of ANCO-1 to inhibit ligand-dependent transcriptional activation by nuclear receptors may the function of p160 coactivators by recruiting to the we have identified a novel family of ankyrin repeats containing ANCO-1 and ANCO-1 was in a yeast two-hybrid screen as a RAC3-interacting protein, ANCO-2 was identified in as a protein related to ANCO-1 interacts with p160 coactivators and corepressors, and it inhibits ligand-dependent transcriptional activation by We that recruitment of by ANCO-1 is likely to the histone acetyltransferase activity in the coactivator to the of transcriptional the proteins represent a novel class of nuclear receptor corepressors that may inhibit ligand-dependent transcription by function of coactivators through recruitment of HDACs. The bHLH-PAS domain of p160 coactivators been to interact with secondary coactivators such as (29Wu X. Li H. Chen J.D. J. Biol. Chem. 2001; 276: 23962-23968Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar), B. Orford R.L. Hurst H.C. Parker M.G. EMBO J. 2002; 21: 4094-4103Crossref PubMed Scopus (198) Google Scholar), and J.H. Li H. Stallcup M.R. Mol. Cell. 2003; 12: 1537-1549Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar), as as other transcription factors E. A.M. 2001; Google Scholar). other proteins that both and domains for binding (29Wu X. Li H. Chen J.D. J. Biol. Chem. 2001; 276: 23962-23968Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar), ANCO-1 binds to the domain in binding to domain also in The interaction ANCO-1 and the PAS domain been by yeast and GST Furthermore, we that ANCO-1 is of interacting with full-length p160 are to The N-terminal domain of the ANCO-1 was found in a nasopharyngeal carcinoma susceptibility protein, and the central region of ANCO-1 was as a tumor in medulloblastoma U. Schneider I. Rossler S. Frauenknecht H. Golbeck A. Lechner B. Eigenstetter G. Zobywalski C. Muller-Weihrich S. Graubner U. Schmid I. Sackerer D. Spath M. Goetz C. Prantl F. Asmuss H.P. Bise K. Mautner J. Int. J. Cancer. 2003; 106: 244-251Crossref PubMed Scopus (49) Google Scholar). it is to that ANCO-1 may as a for the The ANCO-1 gene is at a region that is in cancer U. Schneider I. Rossler S. Frauenknecht H. Golbeck A. Lechner B. Eigenstetter G. Zobywalski C. Muller-Weihrich S. Graubner U. Schmid I. Sackerer D. Spath M. Goetz C. Prantl F. Asmuss H.P. Bise K. Mautner J. Int. J. Cancer. 2003; 106: 244-251Crossref PubMed Scopus (49) Google Scholar, J.A. A.J. E. S. J. M. G.R. G. 2002; PubMed Scopus Google Scholar). the that ANCO-1 may be a of ANCO-1 is the of five ankyrin repeats at the N-terminal repeats are amino acids and involved in protein-protein Sci. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). yeast two-hybrid using the ANCO-1 ankyrin repeats as bait other suggesting that ANCO-1 may play a role in from protein-protein The domain of ankyrin a structure, and the repeats in a large of Among the five ankyrin repeats, the is and it the ankyrin is ankyrin repeats in four Immunofluorescence staining of ANCO-1 shows nuclear foci of ANCO-1 in the is with the of nuclear and its predicted function as a transcriptional of ANCO-1 protein in nuclear foci was it an for in protein-protein through We found that the ANCO-1 nuclear foci are distinct from other known nuclear suggesting that ANCO-1 nuclear foci may represent novel that are likely important for ANCO-1 of ANCO-1 with RAC3 also shows RAC3 was to its D.M. Nawaz Z. O'Malley B.W. Mol. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). it is that ANCO-1 nuclear foci may be with the the that the ANCO-1 foci as protein for coactivators or of ANCO-1 nuclear foci be at of ANCO-1 expression and also in stable clones, suggesting that the ANCO-1 may nuclear The that ANCO-1 is a nuclear protein with p160 coactivators and the that ANCO-1 also binds to corepressors a corepressor function for the reporter assay a of transcriptional activation by ANCO-1 further suggest an of p160 coactivators in transcriptional we that ANCO-1 functions as a transcriptional for NRs by interfering with p160 coactivators through the recruitment of HDACs. we found of ANCO-1 and NRs, suggesting that ANCO-1 may be to by p160 coactivators. be by CREB-binding protein/p300 and as a transcriptional for estrogen receptor H. Lin R.J. Xie W. D. Evans R.M. Cell. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). The GRIP1/TIF2 coactivator also be by protein in to F. Stallcup M.R. Kushner P.J. J. Biol. Chem. 2001; 276: Full Text Full Text PDF PubMed Scopus Google Scholar). coactivator may to recruitment or of the It be to the and sequence of protein-protein among p160 coactivators, corepressors, and We S. E. M. and Yang for J. and A. Chen for and J. D. for on the