title: The histone demethylase Jarid1b (Kdm5b) is a novel component of the Rb pathway and associates with E2f-target genes in MEFs during senescence.
abstract: Senescence is a robust cell cycle arrest controlled by the p53 and Rb pathways that acts as an important barrier to tumorigenesis. Senescence is associated with profound alterations in gene expression, including stable suppression of E2f-target genes by heterochromatin formation. Some of these changes in chromatin composition are orchestrated by Rb. In complex with E2f, Rb recruits chromatin modifying enzymes to E2f target genes, leading to their transcriptional repression. To identify novel chromatin remodeling enzymes that specifically function in the Rb pathway, we used a functional genetic screening model for bypass of senescence in murine cells. We identified the H3K4-demethylase Jarid1b as novel component of the Rb pathway in this screening model. We find that depletion of Jarid1b phenocopies knockdown of Rb1 and that Jarid1b associates with E2f-target genes during cellular senescence. These results suggest a role for Jarid1b in Rb-mediated repression of cell cycle genes during senescence.
authors: Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors: Jeroen H
authors: JH
authors: Nijwening
authors: Ernst-Jan
authors: EJ
authors: Geutjes
authors: Rene
authors: R
authors: Bernards
authors: Roderick L
authors: RL
authors: Beijersbergen
mesh_terms: D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D047468:Immunoprecipitation; D056484:Jumonji Domain-Containing Histone Demethylases; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D016160:Retinoblastoma Protein; D056484:Jumonji Domain-Containing Histone Demethylases; C485614:Kdm5b protein, mouse