REST Repression of Neuronal Genes Requires Components of the hSWI·SNF Complex
A function of the transcription factor REST is to block the expression of neuronal phenotypic traits in non-neuronal cells. Previous studies have shown that REST-mediated repression requires histone deacetylase activity and that recruitment of deacetylases is mediated by two co-repressors, Sin3A and CoREST. In this study, we show that a repressor domain in CoREST interacts with BRG1-associated factor (BAF) 57, a component of the hSWI·SNF complex. In vivo, BAF57 occupies the neuronal sodium channel gene (Nav1.2) promoter, and targeting to this gene requires REST. In addition to BAF57, the ATPase BRG1 and BAF170, other members of the hSWI·SNF complex, are also present in the REST·CoREST repressor complex. Microinjection of specific antibodies against BRG1, BAF57, or BAF170 into Rat1 fibroblasts relieves repression of RE1 reporter genes. Together, our data suggest that ATP-dependent chromatin remodeling, as well as histone deacetylation, is needed for REST-mediated repression. A function of the transcription factor REST is to block the expression of neuronal phenotypic traits in non-neuronal cells. Previous studies have shown that REST-mediated repression requires histone deacetylase activity and that recruitment of deacetylases is mediated by two co-repressors, Sin3A and CoREST. In this study, we show that a repressor domain in CoREST interacts with BRG1-associated factor (BAF) 57, a component of the hSWI·SNF complex. In vivo, BAF57 occupies the neuronal sodium channel gene (Nav1.2) promoter, and targeting to this gene requires REST. In addition to BAF57, the ATPase BRG1 and BAF170, other members of the hSWI·SNF complex, are also present in the REST·CoREST repressor complex. Microinjection of specific antibodies against BRG1, BAF57, or BAF170 into Rat1 fibroblasts relieves repression of RE1 reporter genes. Together, our data suggest that ATP-dependent chromatin remodeling, as well as histone deacetylation, is needed for REST-mediated repression. The acquisition and the maintenance of cell phenotype depend upon precisely controlled transcriptional events. For neurons, intrinsic repressor mechanisms are important for controlling multiple steps in the differentiation program, from neural induction to neural specification. In addition, an extrinsic repression mechanism, which correlates with modification of chromatin structure for at least one gene (1Vandenbergh D.J. Wuenschell C.W. Mori N. Anderson D.J. Neuron. 1989; 3: 507-518Google Scholar), blocks expression of neuronal traits outside the nervous system. The transcriptional repressor, REST (also called NRSF) (2Chong J.A. Tapia-Ramirez J. Kim S. Toledo-Aral J.J. Zheng Y. Boutros M.C. Altshuller Y.M. Frohman M.A. Kraner S.D. Mandel G. Cell. 1995; 80: 949-957Google Scholar, 3Schoenherr C.J. Anderson D.J. Science. 1995; 267: 1360-1363Google Scholar), blocks expression of neuronal-specific genes in non-neuronal cells by binding to a conserved 23-bp sequence, RE1 (repressorelement 1; also called NRSE) (2Chong J.A. Tapia-Ramirez J. Kim S. Toledo-Aral J.J. Zheng Y. Boutros M.C. Altshuller Y.M. Frohman M.A. Kraner S.D. Mandel G. Cell. 1995; 80: 949-957Google Scholar, 3Schoenherr C.J. Anderson D.J. Science. 1995; 267: 1360-1363Google Scholar, 4Chen Z.F. Paquette A.J. Anderson D.J. Nat. Genet. 1998; 20: 136-142Google Scholar, 5Jones F.S. Meech R. Bioessays. 1999; 21: 372-376Google Scholar, 6Paquette A.J. Perez S.E. Anderson D.J. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 12318-12323Google Scholar, 7Ballas N. Battaglioli E. Atouf F. Andres M.E. Chenoweth J. Anderson M.E. Burger C. Moniwa M. Davie J.R. Bowers W.J. Federoff H.J. Rose D.W. Rosenfeld M.G. Brehm P. Mandel G. Neuron. 2001; 31: 353-365Google Scholar). Because ectopic expression of REST target genes, such as voltage-dependent ion channels and synaptic proteins, is likely to have deleterious effects in non-neuronal cells, there has been much interest in determining the long term repressor mechanism underlying REST function. REST is a modular protein that represses via two distinct repressor domains. Repression from the amino terminus is mediated by a Sin3·histone deacetylase (HDAC) 1The abbreviations used are: HDAC, histone deacetylase; BAF, BRG1-associated factor; SANT, SW13/ADA2/NcoR/TFIIIB; HMG, high mobility group; GST, glutathione S-transferase; h, human; AD, activation domain; dox, doxycycline; X-gal, 5-bromo-4-chloro-3-indolyl-β-d-galactoside. complex (8Tapia-Ramirez J. Eggen B.J. Peral-Rubio M.J. Toledo-Aral J.J. Mandel G. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 1177-1182Google Scholar, 9Grimes J.A. Nielsen S.J. Battaglioli E. Miska E.A. Speh J.C. Berry D.L. Atouf F. Holdener B.C. Mandel G. Kouzarides T. J. Biol. Chem. 2000; 275: 9461-9467Google Scholar, 10Huang Y. Myers S.J. Dingledine R. Nat. Neurosci. 1999; 2: 867-872Google Scholar, 11Roopra A. Sharling L. Wood I.C. Briggs T. Bachfischer U. Paquette A.J. Buckley N.J. Mol. Cell. Biol. 2000; 20: 2147-2157Google Scholar, 12Naruse Y. Aoki T. Kojima T. Mori N. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 13691-13696Google Scholar), whereas repression from the carboxyl-terminal domain is mediated by the CoREST protein (7Ballas N. Battaglioli E. Atouf F. Andres M.E. Chenoweth J. Anderson M.E. Burger C. Moniwa M. Davie J.R. Bowers W.J. Federoff H.J. Rose D.W. Rosenfeld M.G. Brehm P. Mandel G. Neuron. 2001; 31: 353-365Google Scholar, 13Andres M.E. Burger C. Peral-Rubio M.J. Battaglioli E. Anderson M.E. Grimes J. Dallman J. Ballas N. Mandel G. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 9873-9878Google Scholar). CoREST is in complexes with class I HDACs (1 and 2) both in non-neuronal and neuronal cell lines (7Ballas N. Battaglioli E. Atouf F. Andres M.E. Chenoweth J. Anderson M.E. Burger C. Moniwa M. Davie J.R. Bowers W.J. Federoff H.J. Rose D.W. Rosenfeld M.G. Brehm P. Mandel G. Neuron. 2001; 31: 353-365Google Scholar, 14You A. Tong J.K. Grozinger C.M. Schreiber S.L. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 1454-1458Google Scholar, 15Humphrey G.W. Wang Y. Russanova V.R. Hirai T. Qin J. Nakatani Y. Howard B.H. J. Biol. Chem. 2001; 276: 6817-6824Google Scholar). Like REST, CoREST contains two repressor domains. The amino-terminal domain coincides with the REST binding site and is dependent upon HDAC activity for repression (7Ballas N. Battaglioli E. Atouf F. Andres M.E. Chenoweth J. Anderson M.E. Burger C. Moniwa M. Davie J.R. Bowers W.J. Federoff H.J. Rose D.W. Rosenfeld M.G. Brehm P. Mandel G. Neuron. 2001; 31: 353-365Google Scholar, 14You A. Tong J.K. Grozinger C.M. Schreiber S.L. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 1454-1458Google Scholar). Trichostatin A treatment, as well as HDAC2 antibody microinjection experiments, suggest that the carboxyl-terminal repressor domain is also associated with HDAC activity (7Ballas N. Battaglioli E. Atouf F. Andres M.E. Chenoweth J. Anderson M.E. Burger C. Moniwa M. Davie J.R. Bowers W.J. Federoff H.J. Rose D.W. Rosenfeld M.G. Brehm P. Mandel G. Neuron. 2001; 31: 353-365Google Scholar). It is not known why REST needs two distinct repressor domains if each recruits HDAC activity. One possibility is that CoREST recruits an additional activity specifically involved in maintaining long term repression. Indeed, it is now very well accepted that multiple covalent and non-covalent chromatin modifications are required for proper gene expression. The best studied covalent modifications occur on histones and include acetylation, methylation, phosphorylation, and ubiquitination (16Cheung P. Allis C.D. Sassone-Corsi P. Cell. 2000; 103: 263-271Google Scholar, 17Wu J. Grunstein M. Trends Biochem. Sci. 2000; 25: 619-623Google Scholar). In particular, hypoacetylated histones have been associated primarily with repressed or silenced genes, and manybona fide co-repressor complexes have been described that contain HDAC activity (18Khochbin S. Verdel A. Lemercier C. Seigneurin-Berny D. Curr. Opin. Genet. Dev. 2001; 11: 162-166Google Scholar). Non-covalent modifications are energy-dependent chromatin modifications made by ATP-dependent chromatin-remodeling complexes, such as the SWI·SNF complex. The mammalian SWI·SNF complex is a family of 2-MDa multisubunit ATP-dependent chromatin-remodeling complexes that exists in a variety of biochemically diverse forms (19Kingston R.E. Narlikar G.J. Genes Dev. 1999; 13: 2339-2352Google Scholar, 20Vignali M. Hassan A.H. Neely K.E. Workman J.L. Mol. Cell. Biol. 2000; 20: 1899-1910Google Scholar). Central to the activity is either the ATPase BRG1 or BRM that serve as the catalytic components. Although ATP-dependent chromatin-remodeling activity was associated originally with transcriptional activation, it has become increasingly clear that remodeling activity is also involved in transcriptional repression. For example, microarray analysis of both yeast and human SWI·SNF mutants result in both repression and de-repression of genes (21Holstege F.C. Jennings E.G. Wyrick J.J. Lee T.I. Hengartner C.J. Green M.R. Golub T.R. Lander E.S. Young R.A. Cell. 1998; 95: 717-728Google Scholar, 22Sudarsanam P. Iyer V.R. Brown P.O. Winston F. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 3364-3369Google Scholar, 23Liu R. Liu H. Chen X. Kirby M. Brown P.O. Zhao K. Cell. 2001; 106: 309-318Google Scholar). More specifically, the human homologue of yeast SWI·SNF (hSWI·SNF) has been implicated in repression of the c-fos gene (24Murphy D.J. Hardy S. Engel D.A. Mol. Cell. Biol. 1999; 19: 2724-2733Google Scholar) and is required for retinoblastoma-mediated repression during the cell cycle (25Zhang H.S. Gavin M. Dahiya A. Postigo A.A., Ma, D. Luo R.X. Harbour J.W. Dean D.C. Cell. 2000; 101: 79-89Google Scholar, 26Strobeck M.W. Knudsen K.E. Fribourg A.F. DeCristofaro M.F. Weissman B.E. Imbalzano A.N. Knudsen E.S. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 7748-7753Google Scholar). The Mi-2·NURD complex contains both HDACs and ATP-dependent chromatin-remodeling components, suggesting that these activities can to transcription in Y. J. Young J. Wang Cell. 1998; 2: Scholar, Y. G. D. Cell. 1998; 95: Scholar). two mammalian co-repressors, and have been in complexes with hSWI·SNF A. Y. H. P. D. Mol. Cell. Biol. Scholar, S. A.J. Imbalzano A.N. R.E. Genes Dev. 2001; Scholar, C. J. J. Biol. Chem. 2000; 275: Scholar). BAF57, a of the hSWI·SNF complex, has been to required for the of the gene M. Zhao K. Chen L. Scholar). a CoREST co-repressor complex also remodeling components, in addition to HDAC, to a specific RE1 sequence, we a in yeast the carboxyl-terminal repressor domain of CoREST as that this domain with a component of the mammalian SWI·SNF complex, the high mobility BAF57 T. Y. S. A. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: Scholar). analysis that as well as REST, was in complexes with two additional hSWI·SNF components, BRG1 and this was in cells by the microinjection of specific antibodies against BRG1, BAF57, or BAF170, repression of reporter genes was BAF57 was associated with the RE1 of the sodium channel gene in vivo, and this in the of REST. suggest that the hSWI·SNF complex an important in REST-mediated repression of neuronal genes, likely ATP-dependent chromatin-remodeling activity. a the binding domain with and the binding to amino and amino of have been described J.A. Nielsen S.J. Battaglioli E. Miska E.A. Speh J.C. Berry D.L. Atouf F. Holdener B.C. Mandel G. Kouzarides T. J. Biol. Chem. 2000; 275: 9461-9467Google Scholar, 13Andres M.E. Burger C. Peral-Rubio M.J. Battaglioli E. Anderson M.E. Grimes J. Dallman J. Ballas N. Mandel G. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 9873-9878Google Scholar). A of the binding domain to CoREST amino amino and amino made by a of CoREST and into with A of the binding domain and CoREST amino and amino by into by and by BAF57 and from and into the in the activation domain of and of BAF57 by and as and and into by The was from and the was described (7Ballas N. Battaglioli E. Atouf F. Andres M.E. Chenoweth J. Anderson M.E. Burger C. Moniwa M. Davie J.R. Bowers W.J. Federoff H.J. Rose D.W. Rosenfeld M.G. Brehm P. Mandel G. Neuron. 2001; 31: 353-365Google Scholar, 9Grimes J.A. Nielsen S.J. Battaglioli E. Miska E.A. Speh J.C. Berry D.L. Atouf F. Holdener B.C. Mandel G. Kouzarides T. J. Biol. Chem. 2000; 275: 9461-9467Google Scholar). The expression was by G. R. BAF57 and in site of by transcription and with in the and of the human BAF57 a was described M.E. Burger C. Peral-Rubio M.J. Battaglioli E. Anderson M.E. Grimes J. Dallman J. Ballas N. Mandel G. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 9873-9878Google Scholar). protein the to that by The yeast used has been described M.E. Burger C. Peral-Rubio M.J. Battaglioli E. Anderson M.E. Grimes J. Dallman J. Ballas N. Mandel G. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 9873-9878Google Scholar). was into with a cell to the activation domain of by on and by for activity. of was by a the and an and not to CoREST. by yeast yeast with either or of CoREST to the binding domain and with either or or of these to the activation domain of as described (7Ballas N. Battaglioli E. Atouf F. Andres M.E. Chenoweth J. Anderson M.E. Burger C. Moniwa M. Davie J.R. Bowers W.J. Federoff H.J. Rose D.W. Rosenfeld M.G. Brehm P. Mandel G. Neuron. 2001; 31: 353-365Google Scholar). cells by addition of to for at and in a and in and and to of a and chromatin was with protein at for chromatin was with of each antibody and and of in at on protein with and was by at and the specific in the by For of an was used to the of the into of the from the was used in the with for the to for by of to for and a at for for each to and the cycle and of and as described M.E. Burger C. Peral-Rubio M.J. Battaglioli E. Anderson M.E. Grimes J. Dallman J. Ballas N. Mandel G. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 9873-9878Google Scholar). In was a from to the The in CoREST in was described M.E. Burger C. Peral-Rubio M.J. Battaglioli E. Anderson M.E. Grimes J. Dallman J. Ballas N. Mandel G. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 9873-9878Google Scholar). cells as described M.E. Burger C. Peral-Rubio M.J. Battaglioli E. Anderson M.E. Grimes J. Dallman J. Ballas N. Mandel G. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 9873-9878Google Scholar) and the with and was to the to a of to the expression of as described (7Ballas N. Battaglioli E. Atouf F. Andres M.E. Chenoweth J. Anderson M.E. Burger C. Moniwa M. Davie J.R. Bowers W.J. Federoff H.J. Rose D.W. Rosenfeld M.G. Brehm P. Mandel G. Neuron. 2001; 31: 353-365Google Scholar). used (2Chong J.A. Tapia-Ramirez J. Kim S. Toledo-Aral J.J. Zheng Y. Boutros M.C. Altshuller Y.M. Frohman M.A. Kraner S.D. Mandel G. Cell. 1995; 80: 949-957Google Scholar) and M.E. Burger C. Peral-Rubio M.J. Battaglioli E. Anderson M.E. Grimes J. Dallman J. Ballas N. Mandel G. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 9873-9878Google Scholar). and as to BAF57 and into and used to for antibody from by was Cell. Scholar). The antibody was against protein amino of and by G. R. was from analysis was Microinjection analysis was as described A.J. Perez S.E. Anderson D.J. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 12318-12323Google Scholar). to the fibroblasts by in for into the of cells at a of In antibody was used in the or was cells by of activity was by with cells of as for to in the at least two with a of cells in each A of the human CoREST amino was to and used as in a yeast with a cell A of that to with not One of the an of amino with the activation The amino to a of BAF57, a known component of the hSWI·SNF ATP-dependent chromatin-remodeling complex, and to the amino by the of the BAF57 gene The terminus of the was distinct from the BAF57 The to an a in amino by a and the The was and was by the and of the human BAF57 these two to the of both BAF57 and a protein of amino of which the amino are to specific for BAF57 and against from the of each The antibody the from as well as the protein The of the in the not Like BAF57, is in human cell lines of distinct both non-neuronal and neuronal cell of cells that the ATPase BRG1 was present in both and suggesting that as well as BAF57, is associated with the hSWI·SNF complex an antibody against an by both the we that the two to not the domains required for the CoREST and the BAF57 proteins, we a yeast A family of mutants of was and for the to with protein in yeast CoREST with in this analysis that specifically with the carboxyl-terminal repressor domain of CoREST amino and in (7Ballas N. Battaglioli E. Atouf F. Andres M.E. Chenoweth J. Anderson M.E. Burger C. Moniwa M. Davie J.R. Bowers W.J. Federoff H.J. Rose D.W. Rosenfeld M.G. Brehm P. Mandel G. Neuron. 2001; 31: 353-365Google Scholar). A family of to the was also and for with CoREST The of to with CoREST amino to the in the the BAF57 not with CoREST in not BAF57 and domains. this result was of a of the we the CoREST and both BAF57 and in an in of BAF57 or and from and on a that in CoREST with with both and not in both BAF57 and are to with CoREST and that the CoREST repressor domain interacts with the domain of the BAF57 interacts with BAF57 in and in by CoREST was and in to that with GST, or to of the that cell from cells a not contain BAF57 to the of the cell the of CoREST and the BAF57 proteins, we BAF57 of a CoREST CoREST from cell by for the of BAF57 and that BAF57 is of the CoREST we to in the CoREST not we our on the in CoREST and that BAF57 and REST in a complex that BAF57 is for REST-mediated repression. Because BAF57 is of the hSWI·SNF complex, we BRG1, the catalytic of the hSWI·SNF complex, and BAF170, an additional hSWI·SNF also associated with REST REST present in and from cell of cells from cells BRG1 BRG1 CoREST is also associated with BRG1 and BAF170 in and REST and CoREST are associated with of the hSWI·SNF complex. two hSWI·SNF complexes have been shown to contain A. Y. H. P. D. Mol. Cell. Biol. Scholar, S. A.J. Imbalzano A.N. R.E. Genes Dev. 2001; Scholar, C. J. J. Biol. Chem. 2000; 275: Scholar), we the possibility that BRG1 also associated with REST a It has been shown that repression mediated by the carboxyl-terminal repressor domain of CoREST is and can by microinjection of HDAC2 antibody (7Ballas N. Battaglioli E. Atouf F. Andres M.E. Chenoweth J. Anderson M.E. Burger C. Moniwa M. Davie J.R. Bowers W.J. Federoff H.J. Rose D.W. Rosenfeld M.G. Brehm P. Mandel G. Neuron. 2001; 31: 353-365Google Scholar). The CoREST and BAF57 this repressor to of the hSWI·SNF complex target HDACs to a repressor complex the repressor domain of cell with and for HDACs and chromatin analysis of the RE1 to associated with this against REST, and BAF57 used to chromatin from cells that not the that the RE1 (7Ballas N. Battaglioli E. Atouf F. Andres M.E. Chenoweth J. Anderson M.E. Burger C. Moniwa M. Davie J.R. Bowers W.J. Federoff H.J. Rose D.W. Rosenfeld M.G. Brehm P. Mandel G. Neuron. 2001; 31: 353-365Google Scholar). the RE1 or in the of The of BAF57 on the RE1 the of hSWI·SNF in REST-mediated repression. The hSWI·SNF complex can present on a to the binding of a specific transcription factor or it can specifically to with a transcription factor Workman J.L. Curr. Opin. Genet. Dev. 2000; Scholar). the targeting of BAF57 to the RE1 upon REST, we of a neuronal cell A.J. Perez S.E. Anderson D.J. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 12318-12323Google Scholar), in which REST expression was of and in which REST was shown to the the RE1 for by BAF57, in the and of REST expression. CoREST BAF57 present on the RE1 in cells the expression of both CoREST and with an histone antibody was used as for chromatin induction of REST expression in the cell REST, and BAF57 to the RE1 site data suggest that BAF57 is to the RE1 upon REST expression. to the induction of REST the chromatin of an gene in vivo, we the of histone to the RE1 in both and chromatin analysis and The of histone in cells was to that of the In Rat1 REST, or with a of The cells a of REST protein not and this likely for the of with and cells. The of of the hSWI·SNF complex with the REST·CoREST complex the of the of this the of REST to an RE1 reporter gene in the of in Rat1 the reporter gene is repressed by the of the REST repressor complex. It has been shown that the reporter gene is by the microinjection of both and antibodies (7Ballas N. Battaglioli E. Atouf F. Andres M.E. Chenoweth J. Anderson M.E. Burger C. Moniwa M. Davie J.R. Bowers W.J. Federoff H.J. Rose D.W. Rosenfeld M.G. Brehm P. Mandel G. Neuron. 2001; 31: 353-365Google Scholar). against BAF57, BRG1, or BAF170 repression of the RE1 reporter gene The of de-repression was for each microinjection and was as the of cells that for in the of cells a Microinjection of antibody not repression. to the possibility that microinjection of antibodies against the hSWI·SNF complex with the transcription we used as a a reporter gene to the RE1 the the RE1 A.J. Perez S.E. Anderson D.J. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 12318-12323Google Scholar). reporter was in and we that the microinjection of BRG1, BAF57, or BAF170 not activity these that REST repression of RE1 reporter gene requires the of of the hSWI·SNF complex. It has been that REST the and CoREST complexes upon during J.A. Nielsen S.J. Battaglioli E. Miska E.A. Speh J.C. Berry D.L. Atouf F. Holdener B.C. Mandel G. Kouzarides T. J. Biol. Chem. 2000; 275: 9461-9467Google Scholar). In this we suggest an additional have an of CoREST with BAF57, a component of the hSWI·SNF ATP-dependent chromatin-remodeling complex. analysis that REST was in complexes with the ATPase BRG1, as well as with BAF170, both intrinsic of the hSWI·SNF complex. Microinjection specific antibodies against the ATPase BRG1, as well as against BAF57 and BAF170, repression from a that these required for repression in this it is that the of two repressor domains in CoREST a for remodeling activity by the carboxyl-terminal repressor suggest that BAF57 the hSWI·SNF complex to the RE1 by binding to CoREST via for BAF57 is with the that specific of the hSWI·SNF complex either the activity of the ATPase S. Narlikar G.J. R.E. Mol. Cell. 1999; 3: Scholar) or involved in the targeting of the complex to specific in chromatin (19Kingston R.E. Narlikar G.J. Genes Dev. 1999; 13: 2339-2352Google Scholar, G.J. R.E. Cell. Scholar). with BAF57 are to the for two other hSWI·SNF J. Scholar) and Y. D. S. B.J. Wang Mol. Cell. Biol. 2000; 20: Scholar). of with the to the recruitment of BRG1 to a specific of target genes controlled by the and J. Scholar). is involved in the targeting of the remodeling complex to genes by the by with the Y. D. S. B.J. Wang Mol. Cell. Biol. 2000; 20: Scholar). In addition to a BAF57 is an to to T. Y. S. A. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: Scholar) that it also to of the of the hSWI·SNF complex with the has been shown to a component of a from cells M.A. D.A. Chenoweth J. Mandel G. R. Proc. Natl. Acad. Sci. U. S. A. Scholar). Like BAF57, also contains a interacts with CoREST is not it a function in CoREST complex. The of multiple of the in the REST·CoREST repressor complex is not to the and domains of BAF57 and domain present in one in the complex is the a domain to other transcriptional and that have from the binding The domain can binding and R. A.F. T. Trends Biochem. Sci. 21: Scholar). CoREST contains two that are required for repression. domain I is required for with REST and is involved in HDAC activity (7Ballas N. Battaglioli E. Atouf F. Andres M.E. Chenoweth J. Anderson M.E. Burger C. Moniwa M. Davie J.R. Bowers W.J. Federoff H.J. Rose D.W. Rosenfeld M.G. Brehm P. Mandel G. Neuron. 2001; 31: 353-365Google Scholar, 14You A. Tong J.K. Grozinger C.M. Schreiber S.L. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 1454-1458Google Scholar). show that domain is involved in the with BAF57, in addition to HDAC activity. least additional of the REST·CoREST complex contain or protein with to A. Tong J.K. Grozinger C.M. Schreiber S.L. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 1454-1458Google Scholar, 15Humphrey G.W. Wang Y. Russanova V.R. Hirai T. Qin J. Nakatani Y. Howard B.H. J. Biol. Chem. 2001; 276: 6817-6824Google Scholar, M.A. D.A. Chenoweth J. Mandel G. R. Proc. Natl. Acad. Sci. U. S. A. Scholar), BAF170 Y. S. A. Genes Dev. Scholar), and HDACs and protein involved in also contains a it is likely that these conserved domains for distinct complexes with components. ATP-dependent chromatin-remodeling activity REST-mediated ATP-dependent chromatin remodeling has been to involved at in gene It can the binding of a transcription factor to binding site by and the it can by a transcription factor to a specific site and recruitment the activity of other in G.J. R.E. Cell. Scholar). In the of the Mi-2·NURD complex, which contains both HDACs and ATP-dependent chromatin-remodeling components, deacetylase activity is dependent upon a result that that remodeling the or the of HDACs to chromatin J.K. R.E. Schreiber S.L. 1998; Scholar). the other and that the activity of ATPase is by the of histone J.W. 3: Scholar). In our study, we show that the recruitment of BAF57 to the RE1 upon expression of the REST. the hSWI·SNF complex the activity of other in the chromatin-remodeling complex, for the HDACs associated with the REST complex. The to complexes with distinct activities for the repression of specific genes has been shown for other transcription G.J. R.E. Cell. Scholar). It has been that chromatin-remodeling activities a that specific of covalent and non-covalent histone modifications for each Allis C.D. 2000; Scholar, T. Allis C.D. Science. 2001; Scholar). The modular structure of REST, and both with that histones and that are involved in ATP-dependent remodeling of an to the histone T. Allis C.D. Science. 2001; Scholar) for neuronal gene repression. S. and for the antibody to CoREST. also the with A. and H.