H3K27me3-rich Genomic Regions Can Function As Silencers to Repress Gene Expression Via Chromatin Interactions

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Jan 30

PMID 33514712

Citations 112

Authors

Yichao Cai

Ying Zhang

Yan Ping Loh

Jia Qi Tng

Mei Chee Lim

Zhendong Cao

Anandhkumar Raju

Erez Lieberman Aiden

Shang Li

Lakshmanan Manikandan

Vinay Tergaonkar

Greg Tucker-Kellogg

Melissa Jane Fullwood

Affiliations

Soon will be listed here.

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.

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