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RNA 聚合酶 II 在终末神经元分化过程中启动 Polycomb 抑制的发育基因。

RNA polymerase II primes Polycomb-repressed developmental genes throughout terminal neuronal differentiation.

机构信息

Epigenetic Regulation and Chromatin Architecture, Max Delbrück Center for Molecular Medicine, Berlin, Germany

Genome Function, MRC London Institute of Medical Sciences (previously MRC Clinical Sciences Centre), London, UK.

出版信息

Mol Syst Biol. 2017 Oct 16;13(10):946. doi: 10.15252/msb.20177754.

DOI:10.15252/msb.20177754
PMID:29038337
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5658700/
Abstract

Polycomb repression in mouse embryonic stem cells (ESCs) is tightly associated with promoter co-occupancy of RNA polymerase II (RNAPII) which is thought to prime genes for activation during early development. However, it is unknown whether RNAPII poising is a general feature of Polycomb repression, or is lost during differentiation. Here, we map the genome-wide occupancy of RNAPII and Polycomb from pluripotent ESCs to non-dividing functional dopaminergic neurons. We find that poised RNAPII complexes are ubiquitously present at Polycomb-repressed genes at all stages of neuronal differentiation. We observe both loss and acquisition of RNAPII and Polycomb at specific groups of genes reflecting their silencing or activation. Strikingly, RNAPII remains poised at transcription factor genes which are silenced in neurons through Polycomb repression, and have major roles in specifying other, non-neuronal lineages. We conclude that RNAPII poising is intrinsically associated with Polycomb repression throughout differentiation. Our work suggests that the tight interplay between RNAPII poising and Polycomb repression not only instructs promoter state transitions, but also may enable promoter plasticity in differentiated cells.

摘要

多梳抑制在小鼠胚胎干细胞（ESCs）中与 RNA 聚合酶 II（RNAPII）的启动子共占据紧密相关，这被认为是在早期发育过程中激活基因的前提。然而，尚不清楚 RNAPII 的前置是否是多梳抑制的一般特征，还是在分化过程中丢失。在这里，我们从多能 ESCs 到非分裂的功能性多巴胺能神经元中绘制了全基因组范围内的 RNAPII 和多梳蛋白的占据图谱。我们发现，在神经元分化的所有阶段，前置的 RNAPII 复合物普遍存在于多梳抑制的基因上。我们观察到 RNAPII 和多梳蛋白在特定基因群中的丢失和获得，反映了它们的沉默或激活。引人注目的是，RNAPII 仍然存在于通过多梳抑制沉默的神经元中的转录因子基因上，并且在指定其他非神经元谱系方面发挥着重要作用。我们得出结论，RNAPII 的前置与分化过程中的多梳抑制紧密相关。我们的工作表明，RNAPII 的前置与多梳抑制之间的紧密相互作用不仅指导了启动子状态的转变，而且还可能使分化细胞中的启动子具有可塑性。

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