期刊
CELL REPORTS
卷 23, 期 6, 页码 1853-1866出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.04.023
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资金
- Swedish Medical Research Council [2015-02368]
- Knut and Alice Wallenbergs Foundation [KAW2015.0268, KAW2016.0006]
- Swedish Cancer Foundation [170196]
- Soderbergs Foundation
- Karolinska Institutet
- Federation of European Biochemical Societies (FEBS) Long-Term Fellowship
- Swedish Research Council [2015-02368] Funding Source: Swedish Research Council
Embryonic stem cells (ESCs) display an abbreviated cell cycle, resulting in a short doubling time and rapid proliferation. The histone variant H2A.X is critical for proliferation of stem cells, although mechanistic insights have remained obscure. Here, we show that H2A.X defines the rate of mouse ESC proliferation independently of the DNA damage response pathway, and it associates with three major chromatin-modifying complexes. Our functional and biochemical analyses demonstrate that H2A.X-associated factors mediate the H2A.X-dependent effect on ESC proliferation and involve the nucleolar remodeling complex (NoRC). A specific H2A.X deposition at rDNA promoters determines the chromatin recruitment of the NoRC, histone modifications, the rRNA transcription, and the rate of proliferation. Collectively, our results suggest that NoRC assembly by H2A.X deposition at rRNA promoters silences transcription, and this represents an important regulatory component for ESC proliferation.
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