RNA polymerase II primes Polycomb-repressed developmental genes throughout terminal neuronal differentiation.
RNA polymerase II primes Polycomb-repressed developmental genes throughout terminal neuronal differentiation.
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DOI：
10.15252/msb.20177754
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发表时间：
2017-10-16
影响因子：
9.9
通讯作者：
Pombo A
中科院分区：
文献类型：
--
作者：
Ferrai C;Torlai Triglia E;Risner-Janiczek JR;Rito T;Rackham OJ;de Santiago I;Kukalev A;Nicodemi M;Akalin A;Li M;Ungless MA;Pombo A
小鼠胚胎干细胞（ESCs）中的多梳抑制与RNA聚合酶II （RNAPII）启动子共占用密切相关，RNAPII被认为是早期发育过程中激活的启动基因。然而，目前尚不清楚RNAPII定位是Polycomb抑制的一般特征，还是在分化过程中丢失。在这里，我们绘制了RNAPII和Polycomb的全基因组占用图谱，从多能ESCs到非分裂功能多巴胺能神经元。我们发现平衡的RNAPII复合物在神经元分化的所有阶段普遍存在于Polycomb‐抑制基因中。我们观察到RNAPII和Polycomb在特定基因组的缺失和获得，反映了它们的沉默或激活。引人注目的是，RNAPII仍然在转录因子基因中保持平衡，这些转录因子基因通过Polycomb抑制在神经元中沉默，并在指定其他非神经元谱系中发挥重要作用。我们得出结论，RNAPII在分化过程中与Polycomb抑制存在内在联系。我们的研究表明，RNAPII定位和Polycomb抑制之间的紧密相互作用不仅指导启动子状态的转变，而且可能使启动子在分化细胞中具有可塑性。
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.
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影响因子：
23.9
作者：
Brookes, Emily;de Santiago, Ines;Hebenstreit, Daniel;Morris, Kelly J.;Carroll, Tom;Xie, Sheila Q.;Stock, Julie K.;Heidemann, Martin;Eick, Dirk;Nozaki, Naohito;Kimura, Hiroshi;Ragoussis, Jiannis;Teichmann, Sarah A.;Pombo, Ana
通讯作者：
Pombo, Ana
影响因子：
8.8
作者：
Gaertner B;Johnston J;Chen K;Wallaschek N;Paulson A;Garruss AS;Gaudenz K;De Kumar B;Krumlauf R;Zeitlinger J
通讯作者：
Zeitlinger J
影响因子：
3.7
作者：
Abranches E;Silva M;Pradier L;Schulz H;Hummel O;Henrique D;Bekman E
通讯作者：
Bekman E
影响因子：
64.8
作者：
Choi J;Huebner AJ;Clement K;Walsh RM;Savol A;Lin K;Gu H;Di Stefano B;Brumbaugh J;Kim SY;Sharif J;Rose CM;Mohammad A;Odajima J;Charron J;Shioda T;Gnirke A;Gygi S;Koseki H;Sadreyev RI;Xiao A;Meissner A;Hochedlinger K
通讯作者：
Hochedlinger K
影响因子：
9.8
作者：
Ferrai C;Xie SQ;Luraghi P;Munari D;Ramirez F;Branco MR;Pombo A;Crippa MP
通讯作者：
Crippa MP