Chromatin Accessibility Dynamics during iPSC Reprogramming
Chromatin Accessibility Dynamics during iPSC Reprogramming
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iPSC 重编程过程中的染色质可及性动态
DOI：
10.1016/j.stem.2017.10.012
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发表时间：
2017-12-07
期刊：
影响因子：
23.9
通讯作者：
Pei, Duanqing
中科院分区：
文献类型：
--
作者：
Li, Dongwei;Liu, Jing;Pei, Duanqing
细胞命运的决定在染色质水平上仍然知之甚少。在这里，我们绘制了诱导多能干细胞过程中的染色质重塑动力学。表达Oct 4-Sox 2-Klf 4（OSK）的MEF的ATAC-seq分析揭示了染色质状态从开放到闭合（OC）和闭合到开放（CO）的动态变化，具有OC的初始爆发和CO的结束激增。OC基因座主要由与体细胞命运相关的基因组成，而CO基因座与多能性相关。已知阻碍重编程的因素/条件会阻止OSK驱动的OC并扭曲OC-CO动力学。虽然CO基因座富含OSK基序，OC基因座没有，这表明染色质闭合的替代机制。Sap 30是一种Sin 3A辅阻遏物复合物，是OC移位所必需的，并有助于减少H3 K27 ac在OC位点的沉积。这些结果揭示了重编程过程中的染色质可及性逻辑，可能适用于其他细胞命运的决定。
Cell-fate decisions remain poorly understood at the chromatin level. Here, we map chromatin remodeling dynamics during induction of pluripotent stem cells. ATAC-seq profiling of MEFs expressing Oct4-Sox2-Klf4 (OSK) reveals dynamic changes in chromatin states shifting from open to closed (OC) and closed to open (CO), with an initial burst of OC and an ending surge of CO. The OC loci are largely composed of genes associated with a somatic fate, while the CO loci are associated with pluripotency. Factors/conditions known to impede reprogramming prevent OSKdriven OC and skew OC-CO dynamics. While the CO loci are enriched for OSK motifs, the OC loci are not, suggesting alternative mechanisms for chromatin closing. Sap30, a Sin3A corepressor complex component, is required for the OC shift andfacilitates reduced H3K27ac deposition at OC loci. These results reveal a chromatin accessibility logic during reprogramming that may apply to other cell-fate decisions.