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Title: H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions
Authors: Cai, Yichao
Zhang, Ying
Loh, Yan Ping
Tng, Jia Qi
Lim, Mei Chee
Cao, Zhendong
Raju, Anandhkumar
Lieberman Aiden, Erez
Li, Shang
Manikandan, Lakshmanan
Tergaonkar, Vinay
Tucker-Kellogg, Greg
Fullwood, Melissa Jane
Keywords: Science::Biological sciences::Molecular biology
Issue Date: 2021
Source: Cai, Y., Zhang, Y., Loh, Y. P., Tng, J. Q., Lim, M. C., Cao, Z., ... Fullwood, M. J. (2021). H3K27me3-rich regions can function as silencers to repress gene expression via chromatin interactions. Nature Communications, 12(719). doi:10.1101/684712v4
Project: NRF-NRFF2012-054 
Journal: Nature Communications 
Abstract: The mechanisms underlying gene repression and silencers are poorly understood. Here we investigate the hypothesis that H3K27me3-rich regions of the genome, defined from clusters of H3K27me3 peaks, may be used to identify silencers that can regulate gene expression via proximity or looping. We find that H3K27me3-rich regions are associated with chromatin interactions and interact preferentially with each other. H3K27me3-rich regions component removal at interaction anchors by CRISPR leads to upregulation of interacting target genes, altered H3K27me3 and H3K27ac levels at interacting regions, and altered chromatin interactions. Chromatin interactions did not change at regions with high H3K27me3, but regions with low H3K27me3 and high H3K27ac levels showed changes in chromatin interactions. Cells where H3K27me3-rich regions knockout also show changes in phenotype associated with cell identity, and altered xenograft tumor growth. Finally, we observe that H3K27me3-rich regions-associated genes and long-range chromatin interactions are susceptible to H3K27me3 depletion. Our results characterize H3K27me3-rich regions and their mechanisms of functioning via looping.
ISSN: 2041-1723
DOI: 10.1101/684712v4
Schools: School of Biological Sciences 
Organisations: Cancer Science Institute of Singapore, National University of Singapore
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR)
Department of Biological Sciences, National University of Singapore
Cancer and Stem Cell Biology Programme, Duke-NUS Medical School
Computational Biology Programme, National University of Singapore
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore
Department of Genetics, Baylor College of Medicine
Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania
Rights: © 2021 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
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