Human THAP7 Is a Chromatin-associated, Histone Tail-binding Protein That Represses Transcription via Recruitment of HDAC3 and Nuclear Hormone Receptor Corepressor

Abstract

The identities of signal transducer proteins that integrate histone hypoacetylation and transcriptional repression are largely unknown. Here we demonstrate that THAP7, an uncharacterized member of the recently identified THAP (Thanatos-associated protein) family of proteins, is ubiquitously expressed, associates with chromatin, and represses transcription. THAP7 binds preferentially to hypoacetylated (un-, mono-, and diacetylated) histone H4 tails in vitro via its C-terminal 77 amino acids. Deletion of this domain, or treatment of cells with the histone deacetylase inhibitor TSA, which leads to histone hyperacetylation, partially disrupts THAP7/chromatin association in living cells. THAP7 coimmunoprecipitates with histone deacetylase 3 (HDAC3) and the nuclear hormone receptor corepressor (NCoR) and represses transcription as a Gal4 fusion protein. Chromatin immunoprecipitation assays demonstrate that these corepressors are recruited to promoters in a THAP7 dependent manner and promote histone H3 hypoacetylation. The conserved THAP domain is a key determinant for full HDAC3 association in vitro, and both the THAP domain and the histone interaction domain are important for the repressive properties of THAP7. Full repression mediated by THAP7 is also dependent on NCoR expression. We hypothesize that THAP7 is a dual function repressor protein that actively targets deacetylation of histone H3 necessary to establish transcriptional repression and functions as a signal transducer of the repressive mark of hypoacetylated histone H4. This is the first demonstration of the transcriptional regulatory properties of a human THAP domain protein, and a critical identification of a potential transducer of the repressive signal of hypoacetylated histone H4 in higher eukaryotes. The identities of signal transducer proteins that integrate histone hypoacetylation and transcriptional repression are largely unknown. Here we demonstrate that THAP7, an uncharacterized member of the recently identified THAP (Thanatos-associated protein) family of proteins, is ubiquitously expressed, associates with chromatin, and represses transcription. THAP7 binds preferentially to hypoacetylated (un-, mono-, and diacetylated) histone H4 tails in vitro via its C-terminal 77 amino acids. Deletion of this domain, or treatment of cells with the histone deacetylase inhibitor TSA, which leads to histone hyperacetylation, partially disrupts THAP7/chromatin association in living cells. THAP7 coimmunoprecipitates with histone deacetylase 3 (HDAC3) and the nuclear hormone receptor corepressor (NCoR) and represses transcription as a Gal4 fusion protein. Chromatin immunoprecipitation assays demonstrate that these corepressors are recruited to promoters in a THAP7 dependent manner and promote histone H3 hypoacetylation. The conserved THAP domain is a key determinant for full HDAC3 association in vitro, and both the THAP domain and the histone interaction domain are important for the repressive properties of THAP7. Full repression mediated by THAP7 is also dependent on NCoR expression. We hypothesize that THAP7 is a dual function repressor protein that actively targets deacetylation of histone H3 necessary to establish transcriptional repression and functions as a signal transducer of the repressive mark of hypoacetylated histone H4. This is the first demonstration of the transcriptional regulatory properties of a human THAP domain protein, and a critical identification of a potential transducer of the repressive signal of hypoacetylated histone H4 in higher eukaryotes. The dynamic nature of chromatin modification clearly remains at the core of the process of transcription. The acetylation of histone H3 and H4 tails is strongly associated with transcriptional activation, whereas hypoacetylated histones are a mark of transcriptionally silent heterochromatin (1Wu J. Grunstein M. Trends Biochem. Sci. 2000; 25: 619-623Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar, 2Grunstein M. Nature. 1997; 389: 349-352Crossref PubMed Scopus (2352) Google Scholar). Consistent with this, proteins that acetylate histones (histone acetyltransferases) are generally involved in transcriptional activation, whereas enzymes that remove acetyl groups from histones (histone deacetylases (HDACs)) 1The abbreviations used are: HDAC, histone deacetylase; CBP, CREB-binding protein; DBD, DNA binding domain; HID, histone interacting domain; INHAT, inhibitor of acetyltransferases; GST, glutathione S-transferase; TK, thymidine kinase; THAP, Thanatos-associated protein; siRNA, small interfering RNA; luc, luciferase; TAF-Iα, template-activating factor-Iα; TAF-Iβ, template-activating factor-Iβ; TSA, trichostatin A. 1The abbreviations used are: HDAC, histone deacetylase; CBP, CREB-binding protein; DBD, DNA binding domain; HID, histone interacting domain; INHAT, inhibitor of acetyltransferases; GST, glutathione S-transferase; TK, thymidine kinase; THAP, Thanatos-associated protein; siRNA, small interfering RNA; luc, luciferase; TAF-Iα, template-activating factor-Iα; TAF-Iβ, template-activating factor-Iβ; TSA, trichostatin A. function in transcriptional repression. In contrast, methylation of histone tails can have both positive and negative effects on transcription (3Zhang Y. Reinberg D. Genes Dev. 2001; 15: 2343-2360Crossref PubMed Scopus (1216) Google Scholar). The number, variety, and interdependence of histone modifications has led to the histone code hypothesis that predicts that modifications acting in combinatorial or sequential fashion on histone tails specify unique downstream functions (4Fischle W. Wang Y. Allis C.D. Curr. Opin. Cell Biol. 2003; 15: 172-183Crossref PubMed Scopus (970) Google Scholar, 5Strahl B.D. Allis C.D. Nature. 2000; 403: 41-45Crossref PubMed Scopus (6448) Google Scholar, 6Jenuwein T. Allis C.D. Science. 2001; 293: 1074-1080Crossref PubMed Scopus (7468) Google Scholar). More recently, a signaling network model of chromatin has been proposed that suggests that multiple chromatin modifications combine to confer bistability, robustness, and adaptability to transcriptional signaling networks (7Schreiber S.L. 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Cell. 2002; 111: Full Text Full Text PDF PubMed Scopus Google Scholar, Cell. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. 2000; PubMed Scopus Google Scholar, Science. 2000; PubMed Scopus Google Scholar, P. P. D. P. J. 2000; PubMed Scopus Google Scholar, 2002; PubMed Scopus Google Scholar). This is to be a critical histones are transcriptionally acetylation also has proposed in to the signaling as higher chromatin by the positive on histone tails and their association with the of DNA and interaction with K. Nature. 1997; 389: PubMed Scopus Google Scholar, K. Curr. Opin. Dev. 2003; PubMed Scopus Google Scholar). and are proteins that bind hypoacetylated histones and have been to transcriptional repression. In at and the silent functions with and to P. K. D. Genes Dev. PubMed Scopus Google Scholar, D. A. A. J. Sci. S. A. 1997; PubMed Scopus Google Scholar, S. A. K. Grunstein M. Genes Dev. 1997; PubMed Scopus Google Scholar). with histone H4 tails that are hypoacetylated by Grunstein M. J. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). In the corepressor with histone H3 and H4 tails via a domain that is also for transcriptional repression Genes Dev. PubMed Scopus Google Scholar). This interaction is by of histone a repression can be The corepressor also with histone deacetylases that are for its function Y. Y. W. Genes Dev. 2000; PubMed Scopus Google Scholar). In higher the or hypoacetylated histones transcriptional repression are largely unknown. We have that TAF-Iα, and bind to histones and from as for the histone and a process we to as histone P. S. A. D. Cell. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, T. P. Y. S. D. J. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). we and have that and with histone deacetylases and can bind to histone are human proteins that can the transcriptionally repressive of histones T. D. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, A.J. Kouzarides T. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). In this we THAP7, a human protein we in an interaction with This protein is a member of a of proteins the THAP domain, a domain to the DNA binding domain of the M. S. T. A. Trends Biochem. Sci. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). are human proteins that the THAP domain, and a of the domain as as its of of this family have been a protein that in a for involved in in cells A. Genes Dev. PubMed Scopus Google and in a for of the protein M. M. Cell. Biol. PubMed Scopus Google Scholar), and a protein that both and M. T. 2003; PubMed Scopus Google Scholar). in and that THAP domain proteins have in transcription M. S. T. A. Trends Biochem. Sci. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar, M. S. Curr. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, Cell. Full Text Full Text PDF PubMed Scopus Google Scholar). transcriptional regulatory properties of member of the THAP domain family have been Here we demonstrate that THAP7 binds to histones and in a manner and binds to histone H4 in an acetylation THAP7 associates with chromatin in living cells and THAP7 represses transcription of and and associates with HDAC3 and This is the first demonstration of chromatin and transcriptional regulatory function of a human THAP family protein. the and with a from human cells the and P. A. D. Cell. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). and these cells and and from these and of the the human protein THAP7. by DNA and with a multiple and a multiple the and by a and and its from the THAP7 and the the the Gal4 the and fusion proteins in and of DNA by In histone binding of histones from cells with a in the of protein and in vitro proteins the in vitro in vitro proteins or histones with fusion proteins from cells in 1 inhibitor and for and proteins on and by and by a and histone H3 binding and Cell and cells or cells a with Gal4 DNA binding of an or in with with and and with to the cells assays to the treatment for or 1 cells in on for 1 inhibitor by at and in 1 and or by cells in and as at a with or with protein and with proteins by and to a with or as histone from or by and with to of the with in vitro THAP7 in 1 inhibitor and with and proteins by and by a as by M. P. Cell. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). In cells in 1 inhibitor 1 of which of at and with with for and at The and the in at the The of in the chromatin by DNA and by to with and histone as or to for by of inhibitor cells in on for for at The with with of to proteins to and as cells or cells an or Gal4 DNA binding and Gal4 to be the cells with Gal4 and Gal4 protein Gal4 or the Gal4 and to the used to of the NCoR cells first with for by with and repressor the from Chromatin cells with for by of for at in at and in chromatin immunoprecipitation 1 for a of at a the in chromatin immunoprecipitation 1 and with protein and of the at for 1 the with histone histone H4 or The by with protein for 3 and with 1 with 1 with 3 1 and with in of of by at DNA and by the of the THAP7 and for and potential proteins, we a as the and a human the interacting the human protein THAP7. THAP7 is amino and a and a at its also a and conserved THAP domain that is in at human proteins, and also in and proteins M. S. T. A. Trends Biochem. Sci. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). The of human THAP7 has at the amino the of the protein, whereas the the of THAP7 has an that a domain, a domain as as a domain The also a domain in the human and proteins is that this of the a that in a fusion protein of these proteins has been to THAP7 is in human and is as and and is in and in the The of this is unknown. THAP7 with in THAP7 in a with the is the function of the recently identified THAP domain proteins, we to the THAP7 protein. binds to we to THAP7 also with histones in In vitro THAP7 with histones from cells and with THAP7 in the of histones whereas the the transcription and nuclear hormone receptor THAP7 with we histones with or proteins used in binding assays are in to both histone H3 and histone to histone or histone that THAP7 binds to and that the interaction is for histones H3 and H4. this interaction dependent histone we used H3 the histone or a the THAP7 to H3 and to the H3 binding to histone H3 that the demonstrate that the histone H3 is necessary and for THAP7 interaction in In histones in the of THAP7 also bind to from cells and to the binding dependent histone we from cells M. P. Cell. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar), the as S. Cell. Biol. PubMed Scopus Google Scholar), and their to bind at a on of the of tails S. Cell. Biol. PubMed Scopus Google Scholar). to histone and histone in a with histones H3 and H4 in as the core histones in the bind to that histone tails are essential for the histone binding properties of THAP7 are mediated by histone we histone H3 and H4 to with in vitro THAP7, and with to both histone H3 and H4 tails We the histone interaction domain of THAP7. this we a of in vitro and THAP7 in with histone H3 or H4 tails in of the THAP7 that the C-terminal 77 amino in bind to histone H3 and histone H4 a this and binding in that the THAP domain is necessary and that the C-terminal 77 amino of THAP7 are necessary and for histone H3 and H4 binding in This is to as the THAP7 with Chromatin in THAP7 associated with and histone tails in vitro, important to demonstrate that THAP7 with chromatin in living cells. that THAP7 is in the in and cells THAP7 with chromatin, we cells with THAP7 or a that to with histones in vitro been used to demonstrate that nuclear is chromatin Genes Dev. 1997; PubMed Scopus Google and to M. P. Cell. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). The of in the chromatin by of DNA and by of proteins that the of core histones that the of the by this are mono-, and as by the of the DNA nuclear 1 and and chromatin to and with protein in and protein protein) and heterochromatin protein in chromatin or nuclear and of from the THAP7 is both in the nuclear and in the chromatin In contrast, the of THAP7, at to THAP7, chromatin with a in the nuclear the chromatin protein the in the that the protein in its nuclear that THAP7 is a protein, and that the C-terminal 77 amino the of THAP7 is an important determinant for this chromatin in cells. THAP7 to H3 and H4 to H4 in histone code hypothesis and signal transducer model predict the existence of cellular proteins that histones in a modification manner (4Fischle W. Wang Y. Allis C.D. Curr. Opin. Cell Biol. 2003; 15: 172-183Crossref PubMed Scopus (970) Google Scholar, 5Strahl B.D. Allis C.D. Nature. 2000; 403: 41-45Crossref PubMed Scopus (6448) Google Scholar, 6Jenuwein T. Allis C.D. Science. 2001; 293: 1074-1080Crossref PubMed Scopus (7468) Google Scholar, S.L. Bernstein B.E. Cell. 2002; 111: 771-778Abstract Full Text Full Text PDF PubMed Scopus (326) Google Scholar). The to or of proteins from chromatin is proposed to a critical role in has recently been that proteins and bind to histone tails in a modification manner T. D. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, A.J. Kouzarides T. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). THAP7 also binds to histone tails in vitro and chromatin in we to THAP7 to histone tails in a modification this we in vitro THAP7 with histone H4 that mono-, or THAP7 to and histone bind or histone H4 This binding to histone H4 is to has been for the dual protein which binds preferentially to histones A. A. T. K. Sci. S. A. 2003; PubMed Scopus Google Scholar), the of the existence of cellular proteins as of chromatin This binding is also from has been for proteins, which can bind to histone H4 T. D. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, A.J. Kouzarides T. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). We THAP7 has a binding for histone H3 binding THAP7 to histone H3 histone histone H3 that is mono-, or at and methylated at lysine 9 This is from has been with proteins, which can bind to histone H3 and methylated to histone H3 T. D. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, A.J. Kouzarides T. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). that the and of acetylation is an important in the of THAP7 association with histone H4 with histone This modification THAP7 binding to the histone H3 also suggests that its acetylation binding to histone H4 is and that THAP7 a dual role in and the transcriptional regulatory of histones H3 and H4. THAP7 associated with and hypoacetylated histone H4 tails histone H4 we that THAP7 with chromatin as as with hypoacetylated this we cells with THAP7 and the cells with or the inhibitor TSA, which leads to histone THAP7 bind to chromatin, be to the protein from of and to in of as to demonstrate the acetylation binding of A. A. T. K. Sci. S. A. 2003; PubMed Scopus Google Scholar). In THAP7 by and to a with in cells with TSA, which histones as by THAP7 with and with with cells with that is associated with chromatin with hypoacetylated In the from THAP7 THAP7 also that is to chromatin THAP7, with demonstrate that THAP7 association with histone H4 tails and chromatin is at partially acetylation and that the domain is an important determinant in chromatin THAP7 with is proposed that in the histones and the hypoacetylated histones are by the Grunstein M. J. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). deacetylation of by of a protein a of establishment and maintenance of transcriptional repression by the in the nuclear hormone receptor corepressor associates with histone deacetylase 3 and histone H4 and functions in a in histone deacetylation and transcriptional repression J. Y. T. J. 2003; PubMed Scopus Google Scholar). We have that THAP7 is a protein that preferentially binds to hypoacetylated histone H4 in on the we that THAP7 with histone THAP7 can also bind to histone is that histone H3 as a for In either association of THAP7 a critical of THAP7 THAP7 associates with we HDAC3 or and either or THAP7 cells. HDAC3 with THAP7 Consistent with the interaction in also HDAC3 in vitro the HDAC3 interacting of THAP7, we THAP7 to HDAC3 to a fusion of the THAP domain the of the protein binding also with the domain that THAP7 associates with HDAC3 in cells and that the the THAP domain have a HDAC3 association THAP7 the THAP domain protein has been in a repression M. S. Curr. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). THAP domain proteins are transcription M. S. T. A. Trends Biochem. Sci. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). is demonstration of transcriptional regulatory properties of or THAP on the in and and that THAP7 associates with chromatin and we that human THAP7 have transcriptional regulatory of the THAP family are largely the of THAP7 on chromatin is unknown. this and to the transcriptional regulatory of THAP7, we and the of a binding domain fusion of THAP7 on a Gal4 DNA binding Consistent with of an association with transcription in a dependent manner and and at the with 1 with and with to an of Gal4 as we a by Gal4 the repression of THAP7, we and the of a fusion of THAP7 or THAP7 in cells. of by with The of and repression for THAP7 is in which is at for Gal4 Deletion of the THAP domain from amino the repression function of THAP7 by Deletion of the from amino also repression by Deletion of both the THAP and repression mediated by are as repressor 1 and and is important to that in the of the THAP7 of transcriptional repression is at to that This repressor domain is with of 3 and in which we that is the histone interacting domain, whereas the THAP domain is the HDAC3 association The HDAC3 association domain and histone binding domain of THAP7 with repression also that the THAP domain function as an association and transcriptional repression The of a a and used to establish the transcriptional repressive function of THAP7 and to the repression of THAP7. the and to THAP7 can transcription in a we the of Gal4 on either of Gal4 and Gal4 have recently been to demonstrate the transcriptional repression and function by and and transcriptional repression by nuclear T. Cell. Biol. 2003; PubMed Scopus Google Scholar, D. J. Biol. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). Gal4 transcription of the Gal4 at the also the Gal4 demonstrate that THAP7 represses transcription in a chromatin The of and the transcriptional repressive function of THAP7. THAP7 with and NCoR for are transcriptional corepressors that with HDAC3 to transcriptional repression that of nuclear hormone M. Curr. Opin. Cell Biol. 2001; PubMed Scopus Google Scholar, Genes Dev. 2000; PubMed Google Scholar, Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, J. J. J. J. 2003; PubMed Scopus Google Scholar). binds to hypoacetylated associates with and histone deacetylation in a J. Y. T. J. 2003; PubMed Scopus Google Scholar). we THAP7 associates with Consistent with of an association HDAC3 and THAP7, we that THAP7 with NCoR in nuclear the of NCoR in transcriptional we cells with NCoR T. Cell. Biol. 2003; PubMed Scopus Google Scholar). We by that NCoR NCoR protein with cells HDAC3 used as a to demonstrate that NCoR is In cells with NCoR we a in repression by Gal4 that NCoR is at partially for transcriptional repression by THAP7. THAP7 HDAC3 and NCoR to and H3 THAP7 associates with HDAC3 and can bind to histone H3 we that THAP7 histone H3 hypoacetylation to this we cells with the Gal4 DNA binding with Gal4 or Gal4 We chromatin immunoprecipitation with histone histone and We the of histone acetylation and of the proteins to the in cells with either Gal4 or Gal4 the are of Gal4 and Gal4 recruited to the used to the of of the Gal4 cells hypoacetylated on histone H3 histone H4 we the of and NCoR at the we a in HDAC3 and NCoR to the in Gal4 cells and with Gal4 in This is with in vitro binding and and suggests that THAP7 represses transcription by HDAC3 and NCoR to promoters to histone In this we THAP7, a member of the identified THAP domain family of proteins M. S. T. A. Trends Biochem. Sci. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). The of this in the demonstration that human THAP7 is a protein and that the THAP domain is important for transcriptional repression. We demonstrate that human THAP7 binds to histones and in a and associates with chromatin in cells. THAP7 binds to mono-, and histone H4 or histone H4 whereas binds to histone H3 tails of their modification status. This is the first that a human THAP domain protein transcriptional regulatory properties and is associated with THAP7 associates with histones in vitro and with chromatin in cells. The tails of histones are for this association in is to that whereas THAP7 a C-terminal domain with to with a domain for histone binding P. S. A. D. Cell. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, T. P. Y. S. D. J. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). In living of the partially disrupts THAP7/chromatin which that the is involved in of THAP7 are also to to chromatin the of the THAP domain of THAP7 and THAP proteins in DNA binding and chromatin important of THAP7 is that binds to mono-, and or histone H4. the binding to the histone H3 tails is to modification status. THAP7 has histone binding properties from that of proteins and TAF-Iβ, which can bind to histone H4 and hypoacetylated histone H3 T. D. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, A.J. Kouzarides T. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). Consistent with these we that THAP7 is from chromatin at in cells with that THAP7 is to chromatin, and is dependent In of a lysine on the histone H4 of the Grunstein M. Cell. Full Text PDF PubMed Scopus Google Scholar). of or of these with can to a in In has been that the regulatory potential of the H3 and H4 is in these lysine S. Cell. Biol. PubMed Scopus Google Scholar). on in vitro binding we hypothesize that THAP7 from histone H4 is to acetylation of or lysine of histone H4. The acetylation H4 interaction the for on histone H4. The of promoters that or on histone H4 is and THAP7 be a to THAP7 can its to hypoacetylated histone H4 a for transcriptional repression for hypoacetylated histone H4. is histone tails and their modifications in THAP7 association in the of chromatin and this would the of histone tails or which is the of the is that suggests that THAP domain proteins have a role in transcription. In the THAP domain in the as its potential role in transcriptional repression M. S. Curr. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). In of THAP domain proteins are transcription and a with a transcription of the family M. S. T. A. Trends Biochem. Sci. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar, A.J. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). THAP domain protein a with to the DNA binding domain of the protein to the THAP domain Sci. S. A. PubMed Scopus Google Scholar). The THAP domain also has to the DNA binding domain of the conserved or of the DNA binding of the J. PubMed Scopus Google Scholar). strongly that THAP domain a and DNA binding we actively in THAP7 binds of in the establish a role of THAP7 in transcriptional repression. the of both and the transcriptional repressive function of THAP7. are transcriptional repression the THAP domain is the association for the C-terminal domain binds to Deletion of either of these in a protein with repressor of both transcriptional repression by THAP7, the of multiple repression in its THAP7 recruits HDAC3 and NCoR to promoters in Gal4 fusion assays and is dependent on NCoR protein expression. we that THAP7 can transcription at in by corepressor proteins to a chromatin domain, and actively histone is also that THAP7 associates with transcription or corepressors as of its the first the transcriptional regulatory role of human THAP7. also for the proposed transcriptional regulatory of and THAP We hypothesize that THAP7 is a THAP7 binds to and hypoacetylated histone H4 tails of histone H4 by histone proteins a to THAP7 from the histone H4 and for transcriptional THAP7 can also bind to histone H3 tails that are or and also bind to DNA to to a to THAP7 the deacetylation of histone via of HDAC3 and THAP7 can and both the THAP domain and the are DNA binding by the THAP domain is for chromatin transcriptional repression. In we a transcriptional regulatory role of the human THAP7 protein and that the THAP domain to transcriptional repression. The of THAP7 to bind histones and with HDAC3 and NCoR a for the establishment of transcriptional repression by THAP7. the of interaction and potential of THAP7 essential to its in also be necessary to demonstrate that THAP7 recruits the corepressors HDAC3 and NCoR to these to transcription. on we predict that THAP domain proteins be involved in transcription and also the role of proteins in chromatin We M. for the NCoR siRNA, and NCoR and for the and W. for histone H3 We also the for important and on the