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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 MOE2014-T3-1-006 NRF-CRP17-2017-02 |
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. | URI: | https://hdl.handle.net/10356/146349 | 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 http://creativecommons.org/licenses/by/4.0/. | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | SBS Journal Articles |
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