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Cell. 2019 Jun 27;178(1):107-121.e18. doi: 10.1016/j.cell.2019.06.001.

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

Author information

1
Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Medical Research Institute, Wuhan University, Wuhan, Hubei 430071, China. Electronic address: xiaorui9@whu.edu.cn.
2
Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
3
Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA; MOE Key Laboratory of Bioinformatics, Tsinghua University, Beijing 100084, China.
4
Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA; School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, China.
5
College of Life Sciences and Institute for Advanced Studies, Wuhan University, Wuhan, Hubei 430072, China.
6
MOE Key Laboratory of Bioinformatics, Tsinghua University, Beijing 100084, China.
7
Medical Research Institute, Wuhan University, Wuhan, Hubei 430071, China.
8
Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health Science Center, Farmington, CT 06030, USA.
9
School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian 361102, China.
10
Institut de Recherches Cliniques de Montréal, Département de Biochimie and Médecine Moléculaire, Université de Montréal, Montréal, QC H2W 1R7, Canada.
11
Program in Computational and Systems Biology, Department of Biology, MIT, Cambridge, MA 02139, USA.
12
MOE Key Laboratory of Bioinformatics, Tsinghua University, Beijing 100084, China; Department of Biological Sciences, Center for Systems Biology, University of Texas, Dallas, TX 75080, USA.
13
Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: xdfu@ucsd.edu.

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.

KEYWORDS:

RBP-TF co-occupancy; RNA-based transcriptional control; RNA-binding proteins; YY1-mediated DNA looping; chromatin binding; functional genomics

PMID:
31251911
DOI:
10.1016/j.cell.2019.06.001

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