title: SUMOylation negatively modulates target gene occupancy of the KDM5B, a histone lysine demethylase.
abstract: The histone lysine demethylase KDM5B plays key roles in gene repression by demethylating trimethylated lysine 4 of histone H3 (H3K4me3), a modification commonly found at the promoter region of actively transcribed genes. KDM5B is known to regulate the expression of genes involved in cell cycle progression; however, little is known about the post-translational modifications that regulate KDM5B. Herein, we report that KDM5B is SUMOylated at lysine residues 242 and 278 and that the ectopic expression of the hPC2 SUMO E3 ligase enhances this SUMOylation. Interestingly, the levels of KDM5B and its SUMOylated forms are regulated during the cell cycle. KDM5B is modulated by RNF4, an E3 ubiquitin ligase that targets SUMO-modified proteins to proteasomal degradation. Digital gene expression analyses showed that cells expressing the SUMOylation-deficient KDM5B harbor repressed mRNA expression profiles of cell cycle and DNA repair genes. Chromatin immunoprecipitations confirmed some of these genes as KDM5B targets, as they displayed reduced H3K4me3 levels in cells ectopically expressing KDM5B. We propose that SUMOylation by hPC2 regulates the activity of KDM5B.
authors: Terry Fox Molecular Oncology Group and the Bloomfield Center for Research on Aging; Sir Mortimer B Davis Jewish General Hospital; Lady Davis Institute for Medical Research; Montréal, QC Canada; Department of Medicine and Oncology; McGill University; Montréal, QC Canada.
authors: Murilo T D
authors: MT
authors: Bueno
authors: Terry Fox Molecular Oncology Group and the Bloomfield Center for Research on Aging; Sir Mortimer B Davis Jewish General Hospital; Lady Davis Institute for Medical Research; Montréal, QC Canada; Department of Medicine and Oncology; McGill University; Montréal, QC Canada.
authors: Stéphane
authors: S
authors: Richard
mesh_terms: D000818:Animals; D002460:Cell Line; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D058207:Sumoylation
chemical_list: C421605:ELAC2 protein, human; D006657:Histones; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C119611:KDM5B protein, human; D008239:Lysine
keywords: KDM5B; RNF4; SUMOylation; gene occupancy; hPC2; lysine demethylase; lysine methylation