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Enhancer formation during cell reprogramming is edited by the chromatin remodeling factor CHD4

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE201801 | GEO | 2024/01/29

REPOSITORIES: GEO

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Enhancer formation during cell reprogramming is edited by the chromatin remodeling factor CHD4 [RNA-Seq]

Project description:Transcription factors induce dynamic chromatin reorganization during cell fate transition. Pioneer transcription factors are defined as their capability to engage chromatin by binding to nucleosomal DNA in closed chromatin and inducing chromatin opening. However, it has been also shown that these activities are context dependent. Only a subset of pioneer factors’ binding sites become open and the rest of binding sites remain closed. The molecular mechanisms of this context dependent action are still largely unknown. Here, we explore dynamic chromatin rearrangement during GATA3 dependent mesenchymal-to-epithelial transition (MET) in breast cancer cells. We found site-specific kinetic differences in chromatin binding, nucleosome remodeling and chromatin opening by the pioneer factor GATA3. We also identified that a chromatin remodeling enzyme, CHD4, negatively regulates the GATA3-mediated chromatin opening. The silencing of CHD4 induces abnormal chromatin opening leading to unnecessary gene expression for MET. Our study suggests the active regulation of chromatin potential by the chromatin remodeling enzyme for successful cellular reprogramming.

2024-01-29 | GSE201798 | GEO

Enhancer formation during cell reprogramming is edited by the chromatin remodeling factor CHD4 [ChIP-Seq]

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Enhancer formation during cell reprogramming is edited by the chromatin remodeling factor CHD4 [MNase-Seq]

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Enhancer formation during cell reprogramming is edited by the chromatin remodeling factor CHD4 [ATAC-Seq]

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Genomic transcription factor binding site selection is edited by the chromatin remodeling factor CHD4.

Project description:Biologically precise enhancer licensing by lineage-determining transcription factors enables activation of transcripts appropriate to biological demand and prevents deleterious gene activation. This essential process is challenged by the millions of matches to most transcription factor binding motifs present in many eukaryotic genomes, leading to questions about how transcription factors achieve the exquisite specificity required. The importance of chromatin remodeling factors to enhancer activation is highlighted by their frequent mutation in developmental disorders and in cancer. Here we determine the roles of CHD4 to enhancer licensing and maintenance in breast cancer cells and during cellular reprogramming. In unchallenged basal breast cancer cells, CHD4 modulates chromatin accessibility at transcription factor binding sites; its depletion leads to altered motif scanning and redistribution of transcription factors to sites not previously occupied. During GATA3-mediated cellular reprogramming, CHD4 activity is necessary to prevent inappropriate chromatin opening and enhancer licensing. Mechanistically, CHD4 competes with transcription factor-DNA interaction by promoting nucleosome positioning over binding motifs. We propose that CHD4 acts as a chromatin proof-reading enzyme that prevents inappropriate gene expression by editing binding site selection by transcription factors.

| S-EPMC10055546 | biostudies-literature

Enhancer formation during cell reprogramming is edited by the chromatin remodeling factor CHD4

Project description:Enhancer formation during cell reprogramming is edited by the chromatin remodeling factor CHD4

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Enhancer formation during cell reprogramming is edited by the chromatin remodeling factor CHD4 [MNase-Seq]

Project description:Enhancer formation during cell reprogramming is edited by the chromatin remodeling factor CHD4 [MNase-Seq]

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Enhancer formation during cell reprogramming is edited by the chromatin remodeling factor CHD4 [ATAC-Seq]

Project description:Enhancer formation during cell reprogramming is edited by the chromatin remodeling factor CHD4 [ATAC-Seq]

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Enhancer formation during cell reprogramming is edited by the chromatin remodeling factor CHD4 [RNA-Seq]

Project description:Enhancer formation during cell reprogramming is edited by the chromatin remodeling factor CHD4 [RNA-Seq]