Genome Function Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
EMBO Rep. 2009 Nov;10(11):1213-9. doi: 10.1038/embor.2009.221. Epub 2009 Oct 16.
The regulation of gene expression programmes is essential for the generation of diverse cell types during development and for adaptation to environmental signals. RNA polymerase II (RNAPII) transcribes genetic information and coordinates the recruitment of accessory proteins that are responsible for the establishment of active chromatin states and transcript maturation. RNAPII is post-translationally modified at active genes during transcription initiation, elongation and termination, and thereby recruits specific histone and RNA modifiers. RNAPII complexes are also located at silent genes in promoter-proximal paused configurations that provide dynamic transcriptional regulation downstream from initiation. In embryonic stem cells, silent developmental regulator genes that are repressed by Polycomb are associated with a form of RNAPII that can elongate through coding regions but that lacks the post-translational modifications that are important for coupling RNA synthesis to co-transcriptional maturation. Here, we discuss the mechanisms through which the transcription of silent genes might be dissociated from productive expression, and the sophisticated interplay between the transcriptional machinery, Polycomb repression and RNA processing.
基因表达程序的调控对于发育过程中产生多样化的细胞类型以及适应环境信号至关重要。RNA 聚合酶 II（RNAPII）转录遗传信息，并协调募集辅助蛋白，这些蛋白负责建立活性染色质状态和转录成熟。在转录起始、延伸和终止过程中，RNAPII 在活性基因上进行翻译后修饰，从而募集特定的组蛋白和 RNA 修饰物。RNAPII 复合物也位于沉默基因的启动子近端暂停构象中，为起始下游的动态转录调控提供了基础。在胚胎干细胞中，被 Polycomb 抑制的沉默发育调节剂基因与一种能够通过编码区延伸但缺乏与 RNA 合成偶联到共转录成熟相关的翻译后修饰的 RNAPII 形式相关联。在这里，我们讨论了沉默基因的转录如何与有功能的表达分离的机制，以及转录机制、Polycomb 抑制和 RNA 加工之间的复杂相互作用。
