Li Zheng, Wang Ming, Zhong Zhenhui, Gallego-Bartolomé Javier, Feng Suhua, Jami-Alahmadi Yasaman, Wang Xinyi, Wohlschlegel James, Bischof Sylvain, Long Jeffrey A, Jacobsen Steven E
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
These authors contributed equally.
bioRxiv. 2023 Jan 10:2023.01.10.523455. doi: 10.1101/2023.01.10.523455.
MOM1 is an factor previously shown to mediate transcriptional silencing independent of major DNA methylation changes. Here we found that MOM1 localizes with sites of RNA-directed DNA methylation (RdDM). Tethering MOM1 with artificial zinc finger to unmethylated promoter led to establishment of DNA methylation and silencing. This process was blocked by mutations in components of the Pol V arm of the RdDM machinery, as well as by mutation of . We found that at some endogenous RdDM sites, MOM1 is required to maintain DNA methylation and a closed chromatin state. In addition, efficient silencing of newly introduced transgenes was impaired by mutation of MOM1 or mutation of genes encoding the MOM1 interacting PIAL1/2 proteins. In addition to RdDM sites, we identified a group of MOM1 peaks at active chromatin near genes that colocalized with MORC6. These findings demonstrate a multifaceted role of MOM1 in genome regulation.
MOM1是一种先前已证明可介导转录沉默而不依赖于主要DNA甲基化变化的因子。在这里，我们发现MOM1定位于RNA指导的DNA甲基化（RdDM）位点。将MOM1与人工锌指连接到未甲基化的启动子上会导致DNA甲基化的建立和沉默。这一过程被RdDM机制的Pol V臂组件中的突变以及 的突变所阻断。我们发现，在一些内源性RdDM位点，MOM1是维持DNA甲基化和封闭染色质状态所必需的。此外，MOM1的突变或编码与MOM1相互作用的PIAL1/2蛋白的基因的突变会损害新引入转基因的有效沉默。除了RdDM位点，我们在与MORC6共定位的基因附近的活性染色质上鉴定出一组MOM1峰。这些发现证明了MOM1在基因组调控中的多方面作用。
