Conserved antagonism between JMJD2A/KDM4A and HP1γ during cell cycle progression - PubMed (original) (raw)

. 2010 Dec 10;40(5):736-48.

doi: 10.1016/j.molcel.2010.11.008.

Andrew Allen, Capucine Van Rechem, Emily Forbes, Michelle Longworth, Katrin Tschöp, Claire Rinehart, Jonathan Quiton, Ryan Walsh, Andrea Smallwood, Nicholas J Dyson, Johnathan R Whetstine

Affiliations

• PMID: 21145482
• DOI: 10.1016/j.molcel.2010.11.008

Free article

Conserved antagonism between JMJD2A/KDM4A and HP1γ during cell cycle progression

Joshua C Black et al. Mol Cell. 2010.

Free article

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.

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Comment in

• Histone demethylation and timely DNA replication.
  Gerace EL, Moazed D. Gerace EL, et al. Mol Cell. 2010 Dec 10;40(5):683-4. doi: 10.1016/j.molcel.2010.11.036. Mol Cell. 2010. PMID: 21145476 Free PMC article.

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