Johnson Whitney L, Straight Aaron F
Department of Biochemistry, Stanford University Medical School, Stanford, CA 94305, United States.
Department of Biochemistry, Stanford University Medical School, Stanford, CA 94305, United States.
Curr Opin Cell Biol. 2017 Jun;46:102-109. doi: 10.1016/j.ceb.2017.05.004. Epub 2017 Jun 11.
The formation of condensed, transcriptionally repressed heterochromatin is essential for controlling gene expression throughout development, silencing parasitic DNA elements, and for genome stability and inheritance. Cells employ diverse mechanisms for controlling heterochromatin states through proteins that modify DNA and histones. An emerging theme is that chromatin-associated RNAs play important roles in regulating heterochromatin proteins by controlling their initial recruitment to chromatin, their stable association with chromatin, their spread along chromatin, or their enzymatic activity. Major challenges for the field include not only identifying regulatory RNAs, but understanding the underlying biochemical mechanisms for how RNAs associate with chromatin, the specificity of interactions between heterochromatin proteins and RNA, and how these binding events manifest in cells to orchestrate RNA-mediated regulation of heterochromatin.
凝聚的、转录抑制性异染色质的形成对于整个发育过程中基因表达的控制、寄生DNA元件的沉默以及基因组的稳定性和遗传至关重要。细胞通过修饰DNA和组蛋白的蛋白质采用多种机制来控制异染色质状态。一个新出现的主题是,染色质相关RNA通过控制异染色质蛋白最初募集到染色质、它们与染色质的稳定结合、它们沿染色质的扩散或它们的酶活性,在调节异染色质蛋白中发挥重要作用。该领域的主要挑战不仅包括识别调控RNA,还包括理解RNA与染色质结合的潜在生化机制、异染色质蛋白与RNA之间相互作用的特异性,以及这些结合事件如何在细胞中表现出来以协调RNA介导的异染色质调控。