期刊
CELL STEM CELL
卷 17, 期 3, 页码 273-286出版社
CELL PRESS
DOI: 10.1016/j.stem.2015.07.022
关键词
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资金
- National Basic Research Program (973 Program) [2012CB911201]
- National Natural Science Foundation of China (NSFC) [91213302, 81330055, 31371508]
- Program of International ST Cooperation [2014DFB30020]
- Science and Technology Planning Project of Guangdong Province [2015B020228002]
- NIGMS [GM095599]
- Welch Foundation [Q-1673]
- C-BASS Shared Resource at Dan L. Duncan Cancer Center [P30CA125123]
- shared Instrument Grant from NIH [1S10RR026550]
In mammals, DNA methylation is essential for protecting repetitive sequences from aberrant transcription and recombination. In some developmental contexts (e.g., preimplantation embryos) DNA is hypomethylated but repetitive elements are not dysregulated, suggesting that alternative protection mechanisms exist. Here we explore the processes involved by investigating the role of the chromatin factors Daxx and Atrx. Using genome-wide binding and transcriptome analysis, we found that Daxx and Atrx have distinct chromatin-binding profiles and are co-enriched at tandem repetitive elements in wild-type mouse ESCs. Global DNA hypomethylation further promoted recruitment of the Daxx/Atrx complex to tandem repeat sequences, including retrotransposons and telomeres. Knockdown of Daxx/Atrx in cells with hypomethylated genomes exacerbated aberrant transcriptional de-repression of repeat elements and telomere dysfunction. Mechanistically, Daxx/Atrx-mediated repression seems to involve Suv39h recruitment and H3K9 trimethylation. Our data therefore suggest that Daxx and Atrx safeguard the genome by silencing repetitive elements when DNA methylation levels are low.
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