Cargando…
Regulation of chromatin accessibility by the histone chaperone CAF-1 sustains lineage fidelity
Cell fate commitment is driven by dynamic changes in chromatin architecture and activity of lineage-specific transcription factors (TFs). The chromatin assembly factor-1 (CAF-1) is a histone chaperone that regulates chromatin architecture by facilitating nucleosome assembly during DNA replication. A...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9054786/ https://www.ncbi.nlm.nih.gov/pubmed/35487911 http://dx.doi.org/10.1038/s41467-022-29730-6 |
_version_ | 1784697269124071424 |
---|---|
author | Franklin, Reuben Guo, Yiming He, Shiyang Chen, Meijuan Ji, Fei Zhou, Xinyue Frankhouser, David Do, Brian T. Chiem, Carmen Jang, Mihyun Blanco, M. Andres Vander Heiden, Matthew G. Rockne, Russell C. Ninova, Maria Sykes, David B. Hochedlinger, Konrad Lu, Rui Sadreyev, Ruslan I. Murn, Jernej Volk, Andrew Cheloufi, Sihem |
author_facet | Franklin, Reuben Guo, Yiming He, Shiyang Chen, Meijuan Ji, Fei Zhou, Xinyue Frankhouser, David Do, Brian T. Chiem, Carmen Jang, Mihyun Blanco, M. Andres Vander Heiden, Matthew G. Rockne, Russell C. Ninova, Maria Sykes, David B. Hochedlinger, Konrad Lu, Rui Sadreyev, Ruslan I. Murn, Jernej Volk, Andrew Cheloufi, Sihem |
author_sort | Franklin, Reuben |
collection | PubMed |
description | Cell fate commitment is driven by dynamic changes in chromatin architecture and activity of lineage-specific transcription factors (TFs). The chromatin assembly factor-1 (CAF-1) is a histone chaperone that regulates chromatin architecture by facilitating nucleosome assembly during DNA replication. Accumulating evidence supports a substantial role of CAF-1 in cell fate maintenance, but the mechanisms by which CAF-1 restricts lineage choice remain poorly understood. Here, we investigate how CAF-1 influences chromatin dynamics and TF activity during lineage differentiation. We show that CAF-1 suppression triggers rapid differentiation of myeloid stem and progenitor cells into a mixed lineage state. We find that CAF-1 sustains lineage fidelity by controlling chromatin accessibility at specific loci, and limiting the binding of ELF1 TF at newly-accessible diverging regulatory elements. Together, our findings decipher key traits of chromatin accessibility that sustain lineage integrity and point to a powerful strategy for dissecting transcriptional circuits central to cell fate commitment. |
format | Online Article Text |
id | pubmed-9054786 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-90547862022-05-01 Regulation of chromatin accessibility by the histone chaperone CAF-1 sustains lineage fidelity Franklin, Reuben Guo, Yiming He, Shiyang Chen, Meijuan Ji, Fei Zhou, Xinyue Frankhouser, David Do, Brian T. Chiem, Carmen Jang, Mihyun Blanco, M. Andres Vander Heiden, Matthew G. Rockne, Russell C. Ninova, Maria Sykes, David B. Hochedlinger, Konrad Lu, Rui Sadreyev, Ruslan I. Murn, Jernej Volk, Andrew Cheloufi, Sihem Nat Commun Article Cell fate commitment is driven by dynamic changes in chromatin architecture and activity of lineage-specific transcription factors (TFs). The chromatin assembly factor-1 (CAF-1) is a histone chaperone that regulates chromatin architecture by facilitating nucleosome assembly during DNA replication. Accumulating evidence supports a substantial role of CAF-1 in cell fate maintenance, but the mechanisms by which CAF-1 restricts lineage choice remain poorly understood. Here, we investigate how CAF-1 influences chromatin dynamics and TF activity during lineage differentiation. We show that CAF-1 suppression triggers rapid differentiation of myeloid stem and progenitor cells into a mixed lineage state. We find that CAF-1 sustains lineage fidelity by controlling chromatin accessibility at specific loci, and limiting the binding of ELF1 TF at newly-accessible diverging regulatory elements. Together, our findings decipher key traits of chromatin accessibility that sustain lineage integrity and point to a powerful strategy for dissecting transcriptional circuits central to cell fate commitment. Nature Publishing Group UK 2022-04-29 /pmc/articles/PMC9054786/ /pubmed/35487911 http://dx.doi.org/10.1038/s41467-022-29730-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Franklin, Reuben Guo, Yiming He, Shiyang Chen, Meijuan Ji, Fei Zhou, Xinyue Frankhouser, David Do, Brian T. Chiem, Carmen Jang, Mihyun Blanco, M. Andres Vander Heiden, Matthew G. Rockne, Russell C. Ninova, Maria Sykes, David B. Hochedlinger, Konrad Lu, Rui Sadreyev, Ruslan I. Murn, Jernej Volk, Andrew Cheloufi, Sihem Regulation of chromatin accessibility by the histone chaperone CAF-1 sustains lineage fidelity |
title | Regulation of chromatin accessibility by the histone chaperone CAF-1 sustains lineage fidelity |
title_full | Regulation of chromatin accessibility by the histone chaperone CAF-1 sustains lineage fidelity |
title_fullStr | Regulation of chromatin accessibility by the histone chaperone CAF-1 sustains lineage fidelity |
title_full_unstemmed | Regulation of chromatin accessibility by the histone chaperone CAF-1 sustains lineage fidelity |
title_short | Regulation of chromatin accessibility by the histone chaperone CAF-1 sustains lineage fidelity |
title_sort | regulation of chromatin accessibility by the histone chaperone caf-1 sustains lineage fidelity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9054786/ https://www.ncbi.nlm.nih.gov/pubmed/35487911 http://dx.doi.org/10.1038/s41467-022-29730-6 |
work_keys_str_mv | AT franklinreuben regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT guoyiming regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT heshiyang regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT chenmeijuan regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT jifei regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT zhouxinyue regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT frankhouserdavid regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT dobriant regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT chiemcarmen regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT jangmihyun regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT blancomandres regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT vanderheidenmatthewg regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT rocknerussellc regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT ninovamaria regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT sykesdavidb regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT hochedlingerkonrad regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT lurui regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT sadreyevruslani regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT murnjernej regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT volkandrew regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity AT cheloufisihem regulationofchromatinaccessibilitybythehistonechaperonecaf1sustainslineagefidelity |