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H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions.
- Source :
-
Nature communications [Nat Commun] 2021 Jan 29; Vol. 12 (1), pp. 719. Date of Electronic Publication: 2021 Jan 29. - Publication Year :
- 2021
-
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.
- Subjects :
- Animals
Cell Line, Tumor
Chromatin genetics
Chromatin Immunoprecipitation Sequencing
Female
Fibroblast Growth Factors genetics
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Gene Knockout Techniques
Histones metabolism
Humans
Insulin-Like Growth Factor II genetics
Mice
RNA-Seq
Xenograft Model Antitumor Assays
Chromatin metabolism
Epigenetic Repression
Histones genetics
Neoplasms genetics
Silencer Elements, Transcriptional genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 33514712
- Full Text :
- https://doi.org/10.1038/s41467-021-20940-y