Cai, Y., Zhang, Y., Loh, Y. P., Tng, J. Q., Lim, M. C., Cao, Z., … Fullwood, M. J. (2021). H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions. Nature Communications, 12(1). doi:10.1038/s41467-021-20940-y
Abstract:
AbstractThe 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.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research / project is supported by the National Research Foundation - NRF Fellowship
Grant Reference no. : NRF-NRFF2012-054
This research / project is supported by the National Research Foundation - Competitive Research Programme
Grant Reference no. : NRF-CRP17-2017-02
This research / project is supported by the Ministry of Education - Academic Research Fund Tier 3
Grant Reference no. : MOE2014-T3-1-006
This research / project is supported by the Ministry of Education - Academic Research Fund Tier 1
Grant Reference no. : NA
This research / project is supported by the Nanyang Technology University (NTU) - Start-up Funds
Grant Reference no. : 001220-00001
This research / project is supported by the National Research Foundation (NRF) / Ministry of Education (MOE) - Research Centres of Excellence initiative
Grant Reference no. : NA