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Pervasive Chromatin-RNA Binding Protein Interactions Enable RNA-Based Regulation of Transcription

Author(s)
Xiao, Rui; Chen, Jia-Yu; Liang, Zhengyu; Luo, Daji; Chen, Geng; Lu, Zhi John; Chen, Yang; Zhou, Bing; Li, Hairi; Du, Xian; Yang, Yang; San, Mingkui; Wei, Xintao; Liu, Wen; Lécuyer, Eric; Graveley, Brenton R.; Yeo, Gene W.; Burge, Christopher B; Zhang, Michael Q.; Zhou, Yu; Fu, Xiang-Dong; ... Show more Show less
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Abstract
Increasing evidence suggests that transcriptional control and chromatin activities at large involve regulatory RNAs, which likely enlist specific RNA-binding proteins (RBPs). Although multiple RBPs have been implicated in transcription control, it has remained unclear how extensively RBPs directly act on chromatin. We embarked on a large-scale RBP ChIP-seq analysis, revealing widespread RBP presence in active chromatin regions in the human genome. Like transcription factors (TFs), RBPs also show strong preference for hotspots in the genome, particularly gene promoters, where their association is frequently linked to transcriptional output. Unsupervised clustering reveals extensive co-association between TFs and RBPs, as exemplified by YY1, a known RNA-dependent TF, and RBM25, an RBP involved in splicing regulation. Remarkably, RBM25 depletion attenuates all YY1-dependent activities, including chromatin binding, DNA looping, and transcription. We propose that various RBPs may enhance network interaction through harnessing regulatory RNAs to control transcription. Nuclear RNA-binding proteins are pervasive at gene promoters, with many directly participating in transcription through functional interaction with specific transcription factors.
Date issued
2019-06
URI
https://hdl.handle.net/1721.1/126119
Department
Massachusetts Institute of Technology. Computational and Systems Biology Program
Journal
Cell
Publisher
Elsevier BV
Citation
Xiao, Rui et al. "Pervasive Chromatin-RNA Binding Protein Interactions Enable RNA-Based Regulation of Transcription." Cell 178, 1 (June 2019): P107-121.e18 © 2019 Elsevier Inc
Version: Author's final manuscript
ISSN
0092-8674

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