Rb interacts with histone deacetylase to repress transcription.
Previously, we found that Rb can actively repress transcription of cell cycle genes by binding and inactivating transcription factors at the promoter. Here, we demonstrate that Rb can also repress transcription of endogenous cell cycle genes containing E2F sites through recruitment of histone deacetylase, which deacetylates histones on the promoter, thereby promoting formation of nucleosomes that inhibit transcription. These two mechanisms of repression by Rb are selective-some promoters and transcription factors are blocked by this recruitment of histone deacetylase, whereas others are resistant to histone deacetylase activity and are repressed directly by inhibition of transcription factors.
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Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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D000256:Adenoviridae / Q000235:genetics; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002453:Cell Cycle / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015967:Gene Expression Regulation, Viral; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000235:genetics; D010006:Osteoblasts / Q000166:cytology / Q000201:enzymology; D011401:Promoter Regions, Genetic / Q000502:physiology; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012097:Repressor Proteins; D016160:Retinoblastoma Protein / Q000737:chemistry / Q000378:metabolism*; D013539:Simian virus 40 / Q000235:genetics; D018139:Simplexvirus / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D051996:Transcription Factor RelA; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000201:enzymology; D000099232:Proto-Oncogene Protein Spi-1
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D013937:Thymidine Kinase; D015534:Trans-Activators; D051996:Transcription Factor RelA; D000099232:Proto-Oncogene Protein Spi-1; C079439:MXD1 protein, human