The MeCP1 complex represses transcription through preferential binding, remodeling, and deacetylating methylated nucleosomes.
Histone deacetylation plays an important role in methylated DNA silencing. Recent studies indicated that the methyl-CpG-binding protein, MBD2, is a component of the MeCP1 histone deacetylase complex. Interestingly, MBD2 is able to recruit the nucleosome remodeling and histone deacetylase, NuRD, to methylated DNA in vitro. To understand the relationship between the MeCP1 complex and the NuRD complex, we purified the MeCP1 complex to homogeneity and found that it contains 10 major polypeptides including MBD2 and all of the known NuRD components. Functional analysis of the purified MeCP1 complex revealed that it preferentially binds, remodels, and deacetylates methylated nucleosomes. Thus, our study defines the MeCP1 complex, and provides biochemical evidence linking nucleosome remodeling and histone deacetylation to methylated gene silencing.
Feng
Q
Q
Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599-7295, USA.
Zhang
Y
Y
D000107:Acetylation; D000251:Adenosine Triphosphatases; D000255:Adenosine Triphosphate / Q000378:metabolism; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002850:Chromatography, Gel; D018899:CpG Islands; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000502:physiology*; D020868:Gene Silencing / Q000502:physiology*; D006367:HeLa Cells / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008745:Methylation; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D009363:Neoplasm Proteins / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014158:Transcription, Genetic / Q000502:physiology*
D001324:Autoantigens; C115323:CHD4 protein, human; D004268:DNA-Binding Proteins; D006657:Histones; C115368:MBD2 protein; D046911:Macromolecular Substances; C489689:MeCP1 histone deacetylase complex, human; D009363:Neoplasm Proteins; D009707:Nucleosomes; D000255:Adenosine Triphosphate; D004247:DNA; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D000251:Adenosine Triphosphatases; D004265:DNA Helicases