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H3K9me blocks transcription factor activity in differentiated cells to ensure tissue integrity

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE167168 | GEO | 2021/08/01

REPOSITORIES: GEO

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H3K9me selectively blocks transcription factor activity and ensures differentiated tissue integrity.

Project description: Not available

| S-EPMC8572725 | biostudies-literature

H3K9me blocks transcription factor activity in differentiated cells to ensure tissue integrity [ATAC-seq]

Project description:Development in multicellular organisms is governed by a carefully orchestrated program of gene expression controlled by both genetic and epigenetic factors1,2. Histone H3 lysine 9 methylation (H3K9me) is the defining modification of heterochromatin, which is thought to have two main functions. It silences satellite repeats and transposable elements to ensure genome stability3, and stabilizes differentiated states by repressing tissue-specific genes4,5. Not surprisingly, the loss of appropriately targeted heterochromatin is associated with cancer, loss of tissue integrity, and aging5-8. How H3K9me restricts transcription is unknown. Here we show that in C. elegans H3K9me2 is required to silence different sets of genes in embryos and differentiated post-mitotic cells. During nematode development H3K9me is lost from genes that define cell-type identity and is gained at genes expressed at prior stages or in alternative tissues. We found that a continuous deposition of H3K9me2 is necessary to maintain silencing in terminally differentiated cells. Its loss leads to DNA decompaction, but this is not sufficient to derepress H3K9me-marked genes. Instead, gene derepression in differentiated tissues requires distinct sets of transcription factors (TF) that aberrantly activate enhancers or promoters. Tissue-specific H3K9me distribution thus contributes critically to cell-type specific TF binding providing a rationale for how a limited set of TFs can control complex organismal development9,10.

2021-08-01 | GSE167165 | GEO