Original Article

< Previous         Next >  
LncRNA Platr22 promotes super-enhancer activity and stem cell pluripotency
Pixi Yan1,† , J. Yuyang Lu1,† , Jing Niu1 , Juntao Gao1 , Michael Q. Zhang1 , Yafei Yin1,2,* , Xiaohua Shen1,*
1Tsinghua-Peking Joint Center for Life Sciences, School of Medicine and School of Life Sciences, Tsinghua University, Beijing, China
2Present address: Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, China
These authors contributed equally to this work.
*Correspondence to:Yafei Yin , Email:yafei@tsinghua.edu.cn Xiaohua Shen , Email:xshen@tsinhua.edu.cn
J Mol Cell Biol, Volume 13, Issue 4, April 2021, 295-313,  https://doi.org/10.1093/jmcb/mjaa056
Keyword: lncRNA, Platr22, super-enhancer, pluripotency

Super-enhancers (SEs) comprise large clusters of enhancers, which are co-occupied by multiple lineage-specific and master transcription factors, and play pivotal roles in regulating gene expression and cell fate determination. However, it is still largely unknown whether and how SEs are regulated by the noncoding portion of the genome. Here, through genome-wide analysis, we found that long noncoding RNA (lncRNA) genes preferentially lie next to SEs. In mouse embryonic stem cells (mESCs), depletion of SE-associated lncRNA transcripts dysregulated the activity of their nearby SEs. Specifically, we revealed a critical regulatory role of the lncRNA gene Platr22 in modulating the activity of a nearby SE and the expression of the nearby pluripotency regulator ZFP281. Through these regulatory events, Platr22 contributes to pluripotency maintenance and proper differentiation of mESCs. Mechanistically, Platr22 transcripts coat chromatin near the SE region and interact with DDX5 and hnRNP-L. DDX5 further recruits p300 and other factors related to active transcription. We propose that these factors assemble into a transcription hub, thus promoting an open and active epigenetic chromatin state. Our study highlights an unanticipated role for a class of lncRNAs in epigenetically controlling the activity and vulnerability to perturbation of nearby SEs for cell fate determination.