Cargando…
Pioneer factor ASCL1 cooperates with the mSWI/SNF complex at distal regulatory elements to regulate human neural differentiation
Pioneer transcription factors are thought to play pivotal roles in developmental processes by binding nucleosomal DNA to activate gene expression, though mechanisms through which pioneer transcription factors remodel chromatin remain unclear. Here, using single-cell transcriptomics, we show that end...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10111863/ https://www.ncbi.nlm.nih.gov/pubmed/36931659 http://dx.doi.org/10.1101/gad.350269.122 |
_version_ | 1785027534781415424 |
---|---|
author | Păun, Oana Tan, Yu Xuan Patel, Harshil Strohbuecker, Stephanie Ghanate, Avinash Cobolli-Gigli, Clementina Llorian Sopena, Miriam Gerontogianni, Lina Goldstone, Robert Ang, Siew-Lan Guillemot, François Dias, Cristina |
author_facet | Păun, Oana Tan, Yu Xuan Patel, Harshil Strohbuecker, Stephanie Ghanate, Avinash Cobolli-Gigli, Clementina Llorian Sopena, Miriam Gerontogianni, Lina Goldstone, Robert Ang, Siew-Lan Guillemot, François Dias, Cristina |
author_sort | Păun, Oana |
collection | PubMed |
description | Pioneer transcription factors are thought to play pivotal roles in developmental processes by binding nucleosomal DNA to activate gene expression, though mechanisms through which pioneer transcription factors remodel chromatin remain unclear. Here, using single-cell transcriptomics, we show that endogenous expression of neurogenic transcription factor ASCL1, considered a classical pioneer factor, defines a transient population of progenitors in human neural differentiation. Testing ASCL1's pioneer function using a knockout model to define the unbound state, we found that endogenous expression of ASCL1 drives progenitor differentiation by cis-regulation both as a classical pioneer factor and as a nonpioneer remodeler, where ASCL1 binds permissive chromatin to induce chromatin conformation changes. ASCL1 interacts with BAF SWI/SNF chromatin remodeling complexes, primarily at targets where it acts as a nonpioneer factor, and we provide evidence for codependent DNA binding and remodeling at a subset of ASCL1 and SWI/SNF cotargets. Our findings provide new insights into ASCL1 function regulating activation of long-range regulatory elements in human neurogenesis and uncover a novel mechanism of its chromatin remodeling function codependent on partner ATPase activity. |
format | Online Article Text |
id | pubmed-10111863 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-101118632023-04-19 Pioneer factor ASCL1 cooperates with the mSWI/SNF complex at distal regulatory elements to regulate human neural differentiation Păun, Oana Tan, Yu Xuan Patel, Harshil Strohbuecker, Stephanie Ghanate, Avinash Cobolli-Gigli, Clementina Llorian Sopena, Miriam Gerontogianni, Lina Goldstone, Robert Ang, Siew-Lan Guillemot, François Dias, Cristina Genes Dev Research Papers Pioneer transcription factors are thought to play pivotal roles in developmental processes by binding nucleosomal DNA to activate gene expression, though mechanisms through which pioneer transcription factors remodel chromatin remain unclear. Here, using single-cell transcriptomics, we show that endogenous expression of neurogenic transcription factor ASCL1, considered a classical pioneer factor, defines a transient population of progenitors in human neural differentiation. Testing ASCL1's pioneer function using a knockout model to define the unbound state, we found that endogenous expression of ASCL1 drives progenitor differentiation by cis-regulation both as a classical pioneer factor and as a nonpioneer remodeler, where ASCL1 binds permissive chromatin to induce chromatin conformation changes. ASCL1 interacts with BAF SWI/SNF chromatin remodeling complexes, primarily at targets where it acts as a nonpioneer factor, and we provide evidence for codependent DNA binding and remodeling at a subset of ASCL1 and SWI/SNF cotargets. Our findings provide new insights into ASCL1 function regulating activation of long-range regulatory elements in human neurogenesis and uncover a novel mechanism of its chromatin remodeling function codependent on partner ATPase activity. Cold Spring Harbor Laboratory Press 2023-03-01 /pmc/articles/PMC10111863/ /pubmed/36931659 http://dx.doi.org/10.1101/gad.350269.122 Text en © 2023 Păun et al.; Published by Cold Spring Harbor Laboratory Press https://creativecommons.org/licenses/by/4.0/This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Papers Păun, Oana Tan, Yu Xuan Patel, Harshil Strohbuecker, Stephanie Ghanate, Avinash Cobolli-Gigli, Clementina Llorian Sopena, Miriam Gerontogianni, Lina Goldstone, Robert Ang, Siew-Lan Guillemot, François Dias, Cristina Pioneer factor ASCL1 cooperates with the mSWI/SNF complex at distal regulatory elements to regulate human neural differentiation |
title | Pioneer factor ASCL1 cooperates with the mSWI/SNF complex at distal regulatory elements to regulate human neural differentiation |
title_full | Pioneer factor ASCL1 cooperates with the mSWI/SNF complex at distal regulatory elements to regulate human neural differentiation |
title_fullStr | Pioneer factor ASCL1 cooperates with the mSWI/SNF complex at distal regulatory elements to regulate human neural differentiation |
title_full_unstemmed | Pioneer factor ASCL1 cooperates with the mSWI/SNF complex at distal regulatory elements to regulate human neural differentiation |
title_short | Pioneer factor ASCL1 cooperates with the mSWI/SNF complex at distal regulatory elements to regulate human neural differentiation |
title_sort | pioneer factor ascl1 cooperates with the mswi/snf complex at distal regulatory elements to regulate human neural differentiation |
topic | Research Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10111863/ https://www.ncbi.nlm.nih.gov/pubmed/36931659 http://dx.doi.org/10.1101/gad.350269.122 |
work_keys_str_mv | AT paunoana pioneerfactorascl1cooperateswiththemswisnfcomplexatdistalregulatoryelementstoregulatehumanneuraldifferentiation AT tanyuxuan pioneerfactorascl1cooperateswiththemswisnfcomplexatdistalregulatoryelementstoregulatehumanneuraldifferentiation AT patelharshil pioneerfactorascl1cooperateswiththemswisnfcomplexatdistalregulatoryelementstoregulatehumanneuraldifferentiation AT strohbueckerstephanie pioneerfactorascl1cooperateswiththemswisnfcomplexatdistalregulatoryelementstoregulatehumanneuraldifferentiation AT ghanateavinash pioneerfactorascl1cooperateswiththemswisnfcomplexatdistalregulatoryelementstoregulatehumanneuraldifferentiation AT cobolligigliclementina pioneerfactorascl1cooperateswiththemswisnfcomplexatdistalregulatoryelementstoregulatehumanneuraldifferentiation AT lloriansopenamiriam pioneerfactorascl1cooperateswiththemswisnfcomplexatdistalregulatoryelementstoregulatehumanneuraldifferentiation AT gerontogiannilina pioneerfactorascl1cooperateswiththemswisnfcomplexatdistalregulatoryelementstoregulatehumanneuraldifferentiation AT goldstonerobert pioneerfactorascl1cooperateswiththemswisnfcomplexatdistalregulatoryelementstoregulatehumanneuraldifferentiation AT angsiewlan pioneerfactorascl1cooperateswiththemswisnfcomplexatdistalregulatoryelementstoregulatehumanneuraldifferentiation AT guillemotfrancois pioneerfactorascl1cooperateswiththemswisnfcomplexatdistalregulatoryelementstoregulatehumanneuraldifferentiation AT diascristina pioneerfactorascl1cooperateswiththemswisnfcomplexatdistalregulatoryelementstoregulatehumanneuraldifferentiation |