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Chromatin opening ability of pioneer factor Pax7 depends on unique isoform and C-terminal domain

Pioneer factors are transcription factors (TFs) that have the unique ability to recognise their target DNA sequences within closed chromatin. Whereas their interactions with cognate DNA is similar to other TFs, their ability to interact with chromatin remains poorly understood. Having previously def...

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Autores principales: Bascunana, Virginie, Pelletier, Audrey, Gouhier, Arthur, Bemmo, Amandine, Balsalobre, Aurelio, Drouin, Jacques
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415112/
https://www.ncbi.nlm.nih.gov/pubmed/37326021
http://dx.doi.org/10.1093/nar/gkad520
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author Bascunana, Virginie
Pelletier, Audrey
Gouhier, Arthur
Bemmo, Amandine
Balsalobre, Aurelio
Drouin, Jacques
author_facet Bascunana, Virginie
Pelletier, Audrey
Gouhier, Arthur
Bemmo, Amandine
Balsalobre, Aurelio
Drouin, Jacques
author_sort Bascunana, Virginie
collection PubMed
description Pioneer factors are transcription factors (TFs) that have the unique ability to recognise their target DNA sequences within closed chromatin. Whereas their interactions with cognate DNA is similar to other TFs, their ability to interact with chromatin remains poorly understood. Having previously defined the modalities of DNA interactions for the pioneer factor Pax7, we have now used natural isoforms of this pioneer as well as deletion and replacement mutants to investigate the Pax7 structural requirements for chromatin interaction and opening. We show that the GL+ natural isoform of Pax7 that has two extra amino acids within the DNA binding paired domain is unable to activate the melanotrope transcriptome and to fully activate a large subset of melanotrope-specific enhancers targeted for Pax7 pioneer action. This enhancer subset remains in the primed state rather than being fully activated, despite the GL+ isoform having similar intrinsic transcriptional activity as the GL– isoform. C-terminal deletions of Pax7 lead to the same loss of pioneer ability, with similar reduced recruitments of the cooperating TF Tpit and of the co-regulators Ash2 and BRG1. This suggests complex interrelations between the DNA binding and C-terminal domains of Pax7 that are crucial for its chromatin opening pioneer ability.
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spelling pubmed-104151122023-08-12 Chromatin opening ability of pioneer factor Pax7 depends on unique isoform and C-terminal domain Bascunana, Virginie Pelletier, Audrey Gouhier, Arthur Bemmo, Amandine Balsalobre, Aurelio Drouin, Jacques Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Pioneer factors are transcription factors (TFs) that have the unique ability to recognise their target DNA sequences within closed chromatin. Whereas their interactions with cognate DNA is similar to other TFs, their ability to interact with chromatin remains poorly understood. Having previously defined the modalities of DNA interactions for the pioneer factor Pax7, we have now used natural isoforms of this pioneer as well as deletion and replacement mutants to investigate the Pax7 structural requirements for chromatin interaction and opening. We show that the GL+ natural isoform of Pax7 that has two extra amino acids within the DNA binding paired domain is unable to activate the melanotrope transcriptome and to fully activate a large subset of melanotrope-specific enhancers targeted for Pax7 pioneer action. This enhancer subset remains in the primed state rather than being fully activated, despite the GL+ isoform having similar intrinsic transcriptional activity as the GL– isoform. C-terminal deletions of Pax7 lead to the same loss of pioneer ability, with similar reduced recruitments of the cooperating TF Tpit and of the co-regulators Ash2 and BRG1. This suggests complex interrelations between the DNA binding and C-terminal domains of Pax7 that are crucial for its chromatin opening pioneer ability. Oxford University Press 2023-06-16 /pmc/articles/PMC10415112/ /pubmed/37326021 http://dx.doi.org/10.1093/nar/gkad520 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene regulation, Chromatin and Epigenetics
Bascunana, Virginie
Pelletier, Audrey
Gouhier, Arthur
Bemmo, Amandine
Balsalobre, Aurelio
Drouin, Jacques
Chromatin opening ability of pioneer factor Pax7 depends on unique isoform and C-terminal domain
title Chromatin opening ability of pioneer factor Pax7 depends on unique isoform and C-terminal domain
title_full Chromatin opening ability of pioneer factor Pax7 depends on unique isoform and C-terminal domain
title_fullStr Chromatin opening ability of pioneer factor Pax7 depends on unique isoform and C-terminal domain
title_full_unstemmed Chromatin opening ability of pioneer factor Pax7 depends on unique isoform and C-terminal domain
title_short Chromatin opening ability of pioneer factor Pax7 depends on unique isoform and C-terminal domain
title_sort chromatin opening ability of pioneer factor pax7 depends on unique isoform and c-terminal domain
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415112/
https://www.ncbi.nlm.nih.gov/pubmed/37326021
http://dx.doi.org/10.1093/nar/gkad520
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