Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-021-20940-y
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 
Issue Date: 29-Jan-2021
Publisher: Nature Research
Citation: 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 (2021-01-29). H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions. Nature Communications 12 (1) : 719. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-021-20940-y
Rights: Attribution 4.0 International
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 with 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. © 2021, The Author(s).
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/231970
ISSN: 2041-1723
DOI: 10.1038/s41467-021-20940-y
Rights: Attribution 4.0 International
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