RRC ID 46571
Author Black JC, Allen A, Van Rechem C, Forbes E, Longworth M, Tschöp K, Rinehart C, Quiton J, Walsh R, Smallwood A, Dyson NJ, Whetstine JR.
Title Conserved antagonism between JMJD2A/KDM4A and HP1γ during cell cycle progression.
Journal Mol Cell
Abstract The KDM4/JMJD2 family of histone demethylases is amplified in human cancers. However, little is known about their physiologic or tumorigenic roles. We have identified a conserved and unappreciated role for the JMJD2A/KDM4A H3K9/36 tridemethylase in cell cycle progression. We demonstrate that JMJD2A protein levels are regulated in a cell cycle-dependent manner and that JMJD2A overexpression increased chromatin accessibility, S phase progression, and altered replication timing of specific genomic loci. These phenotypes depended on JMJD2A enzymatic activity. Strikingly, depletion of the only C. elegans homolog, JMJD-2, slowed DNA replication and increased ATR/p53-dependent apoptosis. Importantly, overexpression of HP1γ antagonized JMJD2A-dependent progression through S phase, and depletion of HPL-2 rescued the DNA replication-related phenotypes in jmjd-2(-/-) animals. Our findings describe a highly conserved model whereby JMJD2A regulates DNA replication by antagonizing HP1γ and controlling chromatin accessibility.
Volume 40(5)
Pages 736-48
Published 2010-12-10
DOI 10.1016/j.molcel.2010.11.008
PII S1097-2765(10)00846-4
PMID 21145482
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Cell Cycle* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Cells, Cultured Chromatin / metabolism* Chromatin Immunoprecipitation Chromosomal Proteins, Non-Histone / antagonists & inhibitors Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism* DNA Replication Flow Cytometry HeLa Cells Humans Jumonji Domain-Containing Histone Demethylases / antagonists & inhibitors Jumonji Domain-Containing Histone Demethylases / metabolism* Transfection
IF 15.584
Times Cited 95
C.elegans tm2966 tm1624 tm853 tm1489