Dynamic Changes in Occupancy of Histone Variant H2A.Z during Induced Somatic Cell Reprogramming.

Dynamic Changes in Occupancy of Histone Variant H2A.Z during Induced Somatic Cell Reprogramming.
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DOI:
10.1155/2016/3162363
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发表时间:
2016
影响因子:
4.3
通讯作者:
Liu H
Liu H
中科院分区:
医学3区
文献类型:
--
作者:
Dong F;Song Z;Yu J;Zhang B;Jiang B;Shen Y;Lu Y;Song C;Cong P;Liu H

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诱导性多能干细胞(iPSC)的发展使得研究细胞重编程的机制成为可能。在这里,我们研究了H2A.Z在诱导重编程过程中的动态分布与染色质免疫沉淀深度测序(ChIP-Seq)。我们发现H2 A. Z倾向于聚集在转录起始位点(TSS)附近,并整合到具有高转录活性的基因中。用H2A.Z掺入的基因进行的GO分析表明,大多数基因参与MEF和第7天样品中的染色质组装或拆卸以及染色质修饰,而不是iPSC。此外,与MEF和iPSC相比,我们在第7天样品中检测到TSS周围的H2A.Z掺入水平最高。在第7天仅掺入基因的GO分析也显示了染色质重塑的功能。因此,我们推测H2A.Z可能负责染色质重塑,以增强转录因子对多能性重要基因的访问。因此,这项研究提供了一个更深入的了解诱导重编程的机制。
The development of induced pluripotent stem cells (iPSCs) has enabled study of the mechanisms underlying cellular reprogramming. Here, we have studied the dynamic distribution of H2A.Z during induced reprogramming with chromatin immunoprecipitation deep sequencing (ChIP-Seq). We found that H2A.Z tended to accumulate around transcription start site (TSS) and incorporate in genes with a high transcriptional activity. GO analysis with H2A.Z incorporated genes indicated that most genes are involved in chromatin assembly or disassembly and chromatin modification both in MEF and Day 7 samples, not in iPSCs. Furthermore, we detected the highest level of incorporation of H2A.Z around TSS in Day 7 samples compared to MEFs and iPSCs. GO analysis with only incorporated genes in Day 7 also displayed the function of chromatin remodeling. So, we speculate H2A.Z may be responsible for chromatin remodeling to enhance the access of transcription factors to genes important for pluripotency. This study therefore provides a deeper understanding of the mechanisms underlying induced reprogramming.