1] Department of Chemistry & Biochemistry, Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, Colorado, USA. [2] BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USA.
Nat Struct Mol Biol. 2013 Nov;20(11):1250-7. doi: 10.1038/nsmb.2679. Epub 2013 Sep 29.
Polycomb repressive complex 2 (PRC2) is a histone methyltransferase required for epigenetic silencing during development and cancer. Long noncoding RNAs (lncRNAs) recruit PRC2 to chromatin, but the general role of RNA in maintaining repressed chromatin is unknown. Here we measure the binding constants of human PRC2 to various RNAs and find comparable affinity for human lncRNAs targeted by PRC2 as for irrelevant transcripts from ciliates and bacteria. PRC2 binding is size dependent, with lower affinity for shorter RNAs. In vivo, PRC2 predominantly occupies repressed genes; PRC2 is also associated with active genes, but most of those are not regulated by PRC2. These findings support a model in which PRC2's promiscuous binding to RNA transcripts allows it to scan for target genes that have escaped repression, thus leading to maintenance of the repressed state. Such RNAs may also provide a decoy for PRC2.
多梳抑制复合物 2（PRC2）是一种组蛋白甲基转移酶，在发育和癌症过程中对于表观遗传沉默是必需的。长非编码 RNA（lncRNA）募集 PRC2 到染色质，但 RNA 在维持被抑制的染色质方面的一般作用尚不清楚。在这里，我们测量了人 PRC2 与各种 RNA 的结合常数，发现与 PRC2 靶向的人类 lncRNA 的亲和力相当，与纤毛虫和细菌的无关转录本的亲和力相当。PRC2 结合具有尺寸依赖性，较短的 RNA 亲和力较低。在体内，PRC2 主要占据被抑制的基因；PRC2 也与活性基因相关，但其中大多数不受 PRC2 调控。这些发现支持了这样一种模型，即 PRC2 对 RNA 转录本的混杂结合使其能够扫描那些逃脱抑制的靶基因，从而导致抑制状态的维持。这些 RNA 也可能为 PRC2 提供一种诱饵。
