A novel mammalian complex containing Sin3B mitigates histone acetylation and RNA polymerase II progression within transcribed loci.
Transcription requires the progression of RNA polymerase II (RNAP II) through a permissive chromatin structure. Recent studies of Saccharomyces cerevisiae have demonstrated that the yeast Sin3 protein contributes to the restoration of the repressed chromatin structure at actively transcribed loci. Yet, the mechanisms underlying the restoration of the repressive chromatin structure at transcribed loci and its significance in gene expression have not been investigated in mammals. We report here the identification of a mammalian complex containing the corepressor Sin3B, the histone deacetylase HDAC1, Mrg15, and the PHD finger-containing Pf1 and show that this complex plays important roles in regulation of transcription. We demonstrate that this complex localizes at discrete loci approximately 1 kb downstream of the transcription start site of transcribed genes, and this localization requires both Pf1's and Mrg15's interaction with chromatin. Inactivation of this mammalian complex promotes increased RNAP II progression within transcribed regions and subsequent increased transcription. Our results define a novel mammalian complex that contributes to the regulation of transcription and point to divergent uses of the Sin3 protein homologues throughout evolution in the modulation of transcription.
Dept. of Pharmacology, NYU Langone Medical Center, 550 First Ave., New York, NY 10016, USA.
Petar
P
Jelinic
Jessica
J
Pellegrino
Gregory
G
David
D000107:Acetylation; D002460:Cell Line; D006367:HeLa Cells; D056284:Histone Deacetylase 1 / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D012319:RNA Polymerase II / Q000378:metabolism*; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
D006657:Histones; D018398:Homeodomain Proteins; C470833:MORF4L1 protein, human; D046912:Multiprotein Complexes; D009707:Nucleosomes; C430869:PHF12 protein, human; D012097:Repressor Proteins; C492042:SIN3B protein, human; D014157:Transcription Factors; D012319:RNA Polymerase II; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1