Accurate annotation of accessible chromatin in mouse and human primordial germ cells
Accurate annotation of accessible chromatin in mouse and human primordial germ cells
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小鼠和人类原始生殖细胞中可及染色质的准确注释
DOI：
10.1038/s41422-018-0096-5
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发表时间：
2018-11-01
期刊：
影响因子：
44.1
通讯作者：
Gao, Shaorong
中科院分区：
文献类型：
--
作者：
Li, Jingyi;Shen, Shijun;Gao, Shaorong
在原始生殖细胞（PGC）发育过程中，广泛而准确的染色质重塑对于遗传信息的世代延续至关重要。在这里，我们报告，远端顺式调控元件（克雷斯）标记的DNA酶I-超敏位点（DHS）在小鼠和人类PGC的发展过程中表现出时间限制的活动。使用DHS地图作为代理，我们准确地定位在小鼠PGCs的多能性转录因子的全基因组结合位点。出乎意料的是，我们发现小鼠雌性减数分裂重组热点可以被DHS捕获，并且我们首次在小鼠雌性PGC中鉴定了12，211个重组热点。与减数分裂的雌性PGC相反，有丝分裂停滞的雄性PGC的染色质通过核转录因子Y（NFY）结合在远端调控区是允许的。此外，我们研究了PGC克雷斯的进化压力，比较基因组分析显示，小鼠和人类PGC克雷斯在进化上是保守的，并且在哺乳动物以外的脊椎动物树中显示出很强的保守性。因此，我们的研究结果揭示了小鼠和人类PGC发育过程中独特的、时间上可接近的染色质构型。
Extensive and accurate chromatin remodeling is essential during primordial germ cell (PGC) development for the perpetuation of genetic information across generations. Here, we report that distalcis-regulatory elements (CREs) marked by DNase I-hypersensitive sites (DHSs) show temporally restricted activities during mouse and human PGC development. Using DHS maps as proxy, we accurately locate the genome-wide binding sites of pluripotency transcription factors in mouse PGCs. Unexpectedly, we found that mouse female meiotic recombination hotspots can be captured by DHSs, and for the first time, we identified 12,211 recombination hotspots in mouse female PGCs. In contrast to that of meiotic female PGCs, the chromatin of mitotic-arrested male PGCs is permissive through nuclear transcription factor Y (NFY) binding in the distal regulatory regions. Furthermore, we examined the evolutionary pressure on PGC CREs, and comparative genomic analysis revealed that mouse and human PGC CREs are evolutionarily conserved and show strong conservation across the vertebrate tree outside the mammals. Therefore, our results reveal unique, temporally accessible chromatin configurations during mouse and human PGC development.