The chromatin remodeling complex NoRC targets HDAC1 to the ribosomal gene promoter and represses RNA polymerase I transcription.
Mammalian chromatin remodeling complexes are involved in both activation and repression of transcription. Here, we show that NoRC, a SNF2h- containing nucleolar chromatin remodeling complex, represses ribosomal gene transcription. NoRC-mediated rDNA silencing was alleviated by trichostatin A, indicating that histone deacetylation is causally involved in silencing. Chromatin immunoprecipitation experiments demonstrate that overexpression of TIP5, the large subunit of NoRC, mediates deacetylation of nucleosomes in the vicinity of the rDNA promoter. Protein-protein interaction assays reveal association of TIP5 with the histone deacetylase HDAC1 in vivo and in vitro. Deletion of the C-terminal PHD finger and bromodomain abolishes the interaction of TIP5 and HDAC1, and abrogates transcriptional repression. The results suggest that NoRC silences the rDNA locus by targeting the SIN3 corepressor complex to the rDNA promoter, thereby establishing a repressed chromatin structure.
Division of Molecular Biology of the Cell II, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany.
Yonggang
Y
Zhou
Raffaella
R
Santoro
Ingrid
I
Grummt
D016475:3T3 Cells; D000107:Acetylation; D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000502:physiology*; D004275:DNA, Ribosomal / Q000235:genetics; D020868:Gene Silencing; D020459:Genes, rRNA; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012318:RNA Polymerase I / Q000037:antagonists & inhibitors*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D015534:Trans-Activators / Q000502:physiology; D014158:Transcription, Genetic; D000092468:Bromodomain Containing Proteins
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004275:DNA, Ribosomal; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D006657:Histones; D046911:Macromolecular Substances; D009097:Multienzyme Complexes; D009707:Nucleosomes; D012318:RNA Polymerase I; D011993:Recombinant Fusion Proteins; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D015534:Trans-Activators; C499051:Baz2a protein, mouse; D000092468:Bromodomain Containing Proteins; C110550:HDAC1 protein, human