Creative Research Institution, Hokkaido University, Sapporo 001-0021 Laboratory for Chromatin Dynamics, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan.
Dev Growth Differ. 2012 Jan;54(1):129-41. doi: 10.1111/j.1440-169X.2011.01310.x. Epub 2011 Dec 12.
Post-translational modifications of histones are critical not only for local regulation of gene expression, but also for higher-order structure of the chromosome and genome organization in general. These modifications enable a preset state to be maintained over subsequent generations and thus provide an epigenetic level of regulation. Heterochromatic regions of the genome are epigenetically regulated to maintain a "silent state" and protein coding genes inserted into these regions are subject to the same epigenetic silencing. The fission yeast Schizosaccharomyces pombe has well characterized regions of heterochromatin and has proven to be a powerful model for elucidation of epigenetic silencing mechanisms. Research in S. pombe led to the breakthrough discovery that epigenetic silencing is not solely a chromatin-driven transcriptional repression and that RNA interference of nascent transcripts can guide epigenetic silencing and associated histone modifications. Over the last 10 years, an eloquent integration of genetic and biochemical studies have greatly propelled our understanding of major players and effector complexes for regulation of RNAi-mediated epigenetic silencing in S. pombe. Here, we review recent research related to regulation of the epigenetic state in S. pombe heterochromatin, focusing specifically on the mechanisms by which transcription and RNA processing interact with the chromatin modification machinery to maintain the epigenetically silent state.
组蛋白的翻译后修饰不仅对于局部基因表达调控至关重要，而且对于染色体的高级结构和基因组组织的整体调控也至关重要。这些修饰使预设状态能够在随后的世代中得以维持，从而提供了一种表观遗传调控水平。基因组的异染色质区域受到表观遗传调控以维持“沉默状态”，并且插入这些区域的蛋白质编码基因也受到相同的表观遗传沉默。裂殖酵母 Schizosaccharomyces pombe 具有特征明显的异染色质区域，并且已被证明是阐明表观遗传沉默机制的强大模型。在 S. pombe 中的研究导致了突破性的发现，即表观遗传沉默不仅仅是染色质驱动的转录抑制，并且新生转录物的 RNA 干扰可以指导表观遗传沉默和相关的组蛋白修饰。在过去的 10 年中，遗传和生化研究的巧妙结合极大地推动了我们对 S. pombe 中 RNAi 介导的表观遗传沉默调控的主要参与者和效应复合物的理解。在这里，我们回顾了与 S. pombe 异染色质中表观遗传状态调控相关的最新研究，特别关注转录和 RNA 加工与染色质修饰机制相互作用以维持表观遗传沉默状态的机制。
