Hierarchical Oct4 Binding in Concert with Primed Epigenetic Rearrangements during Somatic Cell Reprogramming
Hierarchical Oct4 Binding in Concert with Primed Epigenetic Rearrangements during Somatic Cell Reprogramming
复制标题
体细胞重编程过程中分层 Oct4 结合与引发的表观遗传重排相结合
DOI：
10.1016/j.celrep.2016.01.013
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发表时间：
2016-02-16
期刊：
影响因子：
8.8
通讯作者：
Gao, Shaorong
中科院分区：
文献类型：
--
作者：
Chen, Jun;Chen, Xiaolong;Gao, Shaorong
核心多能性因子Oct4通过转录控制在体细胞重编程中起关键作用。在这里，我们分析Oct4占用，表观遗传变化和重编程中的基因表达。我们发现Oct4以分级方式结合到具有引发的表观遗传修饰的靶位点。Oct4结合是时间连续的，很少在结合和未结合之间切换。在整个重编程过程中，大多数启动子的10月4日占用保持不变。相比之下，体细胞特异性增强子在早期和中期被沉默，而干细胞特异性增强子在与细胞命运转变平行的晚期被激活。表观遗传重塑和Oct4结合都有助于高动力增强子签名转换。层次化的Oct4绑定与不同阶段的不同功能主题相关联。总的来说，我们的研究结果提供了一个全面的分子路线图Oct4结合与表观遗传重排和丰富的资源，为未来的重编程研究。
The core pluripotency factor Oct4 plays key roles in somatic cell reprogramming through transcriptional control. Here, we profile Oct4 occupancy, epigenetic changes, and gene expression in reprogramming. We find that Oct4 binds in a hierarchical manner to target sites with primed epigenetic modifications. Oct4 binding is temporally continuous and seldom switches between bound and unbound. Oct4 occupancy in most of promoters is maintained throughout the entire reprogramming process. In contrast, somatic cell-specific enhancers are silenced in the early and intermediate stages, whereas stem cell-specific enhancers are activated in the late stage in parallel with cell fate transition. Both epigenetic remodeling and Oct4 binding contribute to the hyperdynamic enhancer signature transitions. The hierarchical Oct4 bindings are associated with distinct functional themes at different stages. Collectively, our results provide a comprehensive molecular roadmap of Oct4 binding in concert with epigenetic rearrangements and rich resources for future reprogramming studies.