| 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
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| Resource |
| C.elegans |
tm2966
tm1624
tm853
tm1489 |
