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Genomic transcription factor binding site selection is edited by the chromatin remodeling factor CHD4
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 motif...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055546/ https://www.ncbi.nlm.nih.gov/pubmed/36993416 http://dx.doi.org/10.21203/rs.3.rs-2587918/v1 |
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author | Saotome, Mika Poduval, Deepak Balakrishnan Grimm, Sara A. Nagornyuk, Aerica Gunarathna, Sakuntha Shimbo, Takashi Wade, Paul A. Takaku, Motoki |
author_facet | Saotome, Mika Poduval, Deepak Balakrishnan Grimm, Sara A. Nagornyuk, Aerica Gunarathna, Sakuntha Shimbo, Takashi Wade, Paul A. Takaku, Motoki |
author_sort | Saotome, Mika |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-10055546 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
spelling | pubmed-100555462023-03-30 Genomic transcription factor binding site selection is edited by the chromatin remodeling factor CHD4 Saotome, Mika Poduval, Deepak Balakrishnan Grimm, Sara A. Nagornyuk, Aerica Gunarathna, Sakuntha Shimbo, Takashi Wade, Paul A. Takaku, Motoki Res Sq Article 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. American Journal Experts 2023-03-15 /pmc/articles/PMC10055546/ /pubmed/36993416 http://dx.doi.org/10.21203/rs.3.rs-2587918/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Saotome, Mika Poduval, Deepak Balakrishnan Grimm, Sara A. Nagornyuk, Aerica Gunarathna, Sakuntha Shimbo, Takashi Wade, Paul A. Takaku, Motoki Genomic transcription factor binding site selection is edited by the chromatin remodeling factor CHD4 |
title | Genomic transcription factor binding site selection is edited by the chromatin remodeling factor CHD4 |
title_full | Genomic transcription factor binding site selection is edited by the chromatin remodeling factor CHD4 |
title_fullStr | Genomic transcription factor binding site selection is edited by the chromatin remodeling factor CHD4 |
title_full_unstemmed | Genomic transcription factor binding site selection is edited by the chromatin remodeling factor CHD4 |
title_short | Genomic transcription factor binding site selection is edited by the chromatin remodeling factor CHD4 |
title_sort | genomic transcription factor binding site selection is edited by the chromatin remodeling factor chd4 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055546/ https://www.ncbi.nlm.nih.gov/pubmed/36993416 http://dx.doi.org/10.21203/rs.3.rs-2587918/v1 |
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