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H3K9me selectively blocks transcription factor activity and ensures differentiated tissue integrity
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H3K9me selectively blocks transcription factor activity and ensures differentiated tissue integrity
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Journal Article
H3K9me selectively blocks transcription factor activity and ensures differentiated tissue integrity
2021
Overview
The developmental role of histone H3K9 methylation (H3K9me), which typifies heterochromatin, remains unclear. In
Caenorhabditis elegans
, loss of H3K9me leads to a highly divergent upregulation of genes with tissue and developmental-stage specificity. During development H3K9me is lost from differentiated cell type-specific genes and gained at genes expressed in earlier developmental stages or other tissues. The continuous deposition of H3K9me2 by the SETDB1 homolog MET-2 after terminal differentiation is necessary to maintain repression. In differentiated tissues, H3K9me ensures silencing by restricting the activity of a defined set of transcription factors at promoters and enhancers. Increased chromatin accessibility following the loss of H3K9me is neither sufficient nor necessary to drive transcription. Increased ATAC-seq signal and gene expression correlate at a subset of loci positioned away from the nuclear envelope, while derepressed genes at the nuclear periphery remain poorly accessible despite being transcribed. In conclusion, H3K9me deposition can confer tissue-specific gene expression and maintain the integrity of terminally differentiated muscle by restricting transcription factor activity.
Gasser and colleagues report that H3K9me2 and H3K9me3 repress lineage-specific and germline genes by restricting the activity of a subset of transcription factors in terminally differentiated
Caenorhabditis
elegans
tissues.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 38/39
/ 64/11
/ 82/51
/ Animals
/ Animals, Genetically Modified
/ Biomedical and Life Sciences
/ Caenorhabditis elegans - genetics
/ Caenorhabditis elegans - metabolism
/ Caenorhabditis elegans Proteins - genetics
/ Caenorhabditis elegans Proteins - metabolism
/ Chromatin Assembly and Disassembly
/ Chromatin Immunoprecipitation Sequencing
/ Genes
/ Histone-Lysine N-Methyltransferase - genetics
/ Histone-Lysine N-Methyltransferase - metabolism
/ Histones
/ Homology
/ Muscles
/ Post-translational modification
/ Protein Processing, Post-Translational
/ Tissues
