A core chromatin remodeling factor instructs global chromatin signaling through multivalent reading of nucleosome codes.
ATP-dependent NuRD repressor complexes involve combinatorial assembly of its subunits. However, the mechanism of gene transcription by MTA1/NuRD remains enigmatic. Here we report that MTA1 methylation by G9a methytransferase and demethylation by LSD1 determines the nucleosome remodeling and transcriptional outcome. Contrary to the current static repressor model of the NuRD complex, we discovered that MTA1 association with nucleosomes and corepressor/coactivator complexes is dynamic. While methylated MTA1 is required for the NuRD repressor complex, demethylated MTA1 recognizes the bivalent histone H3K4-AcK9 mark and recruits coactivator NURF-trithorax remodeling complex in a signaling-dependent manner. MTA1's lysine 532 methylation represents a molecular switch as methylated and demethylated MTA1 nucleate NuRD or NURF complexes with opposite functions in a cyclical manner. In addition, MTA1 possesses an inherent histone amplifier activity with an instructive role in impacting the epigenetic landscape, providing a new perspective to the molecular governance of dual coregulator functions of a master coregulator.
Department of Biochemistry and Molecular Biology, McCormick Genomic and Proteomic Center, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA.
Sujit S
SS
Nair
Da-Qiang
DQ
Li
Rakesh
R
Kumar
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D042002:Chromatin Assembly and Disassembly; D044127:Epigenesis, Genetic; D006367:HeLa Cells; D006649:Histocompatibility Antigens / Q000378:metabolism; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D056466:Histone Demethylases / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D015534:Trans-Activators
D001324:Autoantigens; C115323:CHD4 protein, human; D006649:Histocompatibility Antigens; D006657:Histones; C089320:MTA1 protein, human; D009707:Nucleosomes; D012097:Repressor Proteins; D015534:Trans-Activators; D056466:Histone Demethylases; C495195:KDM1A protein, human; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex