启动子靶向的小激活 RNA 改变核小体定位。

Promoter-Targeted Small Activating RNAs Alter Nucleosome Positioning.

机构信息

Department of Biology, Kunming University, Kunming, China.

Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.

出版信息

Adv Exp Med Biol. 2017;983:53-61. doi: 10.1007/978-981-10-4310-9_4.

DOI:10.1007/978-981-10-4310-9_4

PMID:28639191

Abstract

Epigenetic modification of target promoters has been identified as a mechanism underlying RNA activation (RNAa) induced by promoter-targeting small activating RNAs (saRNAs), but it is unclear how the chromosomal environment influences gene expression. In a study of the activation of the OCT4, SOX2, and NANOG genes by saRNAs, we found that saRNA targeting induced nucleosome-depleted region (NDRs) and the accumulation of RNA polymerase II (RNAPII) near or at the saRNA target sites. Additionally, promoters containing certain cis-regulatory elements such as the TATA box and CpG islands (CGIs) appeared to be more susceptible to RNAa. These results provide novel insight into the mechanism underlying RNAa in that saRNAs induce NDRs in the target promoter to remove nucleosome barriers between RNAPII-binding sites and the transcription start site (TSS), resulting in rapid assembly of transcription preinitiation complex (PIC) and subsequent activation of transcription.

摘要

靶启动子的表观遗传修饰已被确定为启动子靶向小分子激活 RNA（saRNA）诱导的 RNA 激活（RNAa）的机制，但尚不清楚染色体环境如何影响基因表达。在一项针对 saRNA 诱导的 OCT4、SOX2 和 NANOG 基因激活的研究中，我们发现 saRNA 靶向诱导核小体缺失区域（NDR）和 RNA 聚合酶 II（RNAPII）在 saRNA 靶位点附近或处的积累。此外，包含某些顺式调控元件的启动子，如 TATA 盒和 CpG 岛（CGI），似乎更容易受到 RNAa 的影响。这些结果为 RNAa 的作用机制提供了新的见解，即 saRNA 在靶启动子中诱导 NDR，以去除 RNAPII 结合位点与转录起始位点（TSS）之间的核小体障碍，导致转录起始前复合物（PIC）的快速组装和随后的转录激活。