論文 - 詳細
| RRC ID | 46571 |
|---|---|
| 著者 | 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. |
| タイトル | Conserved antagonism between JMJD2A/KDM4A and HP1γ during cell cycle progression. |
| ジャーナル | 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. |
| 巻・号 | 40(5) |
| ページ | 736-48 |
| 公開日 | 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 |
| 引用数 | 95 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm2966 tm1624 tm853 tm1489 |