PHF2-mediated H3K9me balance orchestrates heterochromatin stability and neural progenitor proliferation

Heterochromatin stability is crucial for progenitor proliferation during early neurogenesis. It relays on the maintenance of local hubs of H3K9me. However, understanding the formation of efficient localized levels of H3K9me remains limited. To address this question, we used neural stem cells to anal...

Descripción completa

Detalles Bibliográficos
Autores: Aguirre Infantes, Samuel, Pappa, Stella, Padilla, Natàlia, Iacobucci, Simona, Nacht, Ana Silvina, Vicent, Guillermo P., Jordan, Albert, Cruz, Xavier de la, Martínez-Balbás, Marian
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/372107
Acceso en línea:http://hdl.handle.net/10261/372107
Access Level:acceso abierto
Palabra clave:PHF2
Heterochromatin Integrity
Histone Demethylation
Neural Stem Cells
DNA damage
id ES_3eeafc80f34b741fca29007f62dcf252
oai_identifier_str oai:digital.csic.es:10261/372107
network_acronym_str ES
network_name_str España
repository_id_str
spelling PHF2-mediated H3K9me balance orchestrates heterochromatin stability and neural progenitor proliferationAguirre Infantes, SamuelPappa, StellaPadilla, NatàliaIacobucci, SimonaNacht, Ana SilvinaVicent, Guillermo P.Jordan, AlbertCruz, Xavier de laMartínez-Balbás, MarianPHF2Heterochromatin IntegrityHistone DemethylationNeural Stem CellsDNA damageHeterochromatin stability is crucial for progenitor proliferation during early neurogenesis. It relays on the maintenance of local hubs of H3K9me. However, understanding the formation of efficient localized levels of H3K9me remains limited. To address this question, we used neural stem cells to analyze the function of the H3K9me2 demethylase PHF2, which is crucial for progenitor proliferation. Through mass-spectroscopy and genome-wide assays, we show that PHF2 interacts with heterochromatin components and is enriched at pericentromeric heterochromatin (PcH) boundaries where it maintains transcriptional activity. This binding is essential for silencing the satellite repeats, preventing DNA damage and genome instability. PHF2’s depletion increases the transcription of heterochromatic repeats, accompanied by a decrease in H3K9me3 levels and alterations in PcH organization. We further show that PHF2’s PHD and catalytic domains are crucial for maintaining PcH stability, thereby safeguarding genome integrity. These results highlight the multifaceted nature of PHF2’s functions in maintaining heterochromatin stability and regulating gene expression during neural development. Our study unravels the intricate relationship between heterochromatin stability and progenitor proliferation during mammalian neurogenesis.This study was supported by grants BFU2015-69248-P, PGC2018-096082-B-I00 and PID2021-125862NB-I00 to MAMB from the Spanish Ministry of Economy to MAMB, FPI grant PRE2019-087498 to SAI.Peer reviewedSpringerMinisterio de Economía y Competitividad (España)Ministerio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Ministerio de Ciencia e Innovación (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/372107reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO//BFU2015-69248-Pinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-096082-B-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-125862NB-I00The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1038/s44319-024-00178-7https://doi.org/10.1038/s44319-024-00178-7Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3721072026-05-22T06:33:51Z
dc.title.none.fl_str_mv PHF2-mediated H3K9me balance orchestrates heterochromatin stability and neural progenitor proliferation
title PHF2-mediated H3K9me balance orchestrates heterochromatin stability and neural progenitor proliferation
spellingShingle PHF2-mediated H3K9me balance orchestrates heterochromatin stability and neural progenitor proliferation
Aguirre Infantes, Samuel
PHF2
Heterochromatin Integrity
Histone Demethylation
Neural Stem Cells
DNA damage
title_short PHF2-mediated H3K9me balance orchestrates heterochromatin stability and neural progenitor proliferation
title_full PHF2-mediated H3K9me balance orchestrates heterochromatin stability and neural progenitor proliferation
title_fullStr PHF2-mediated H3K9me balance orchestrates heterochromatin stability and neural progenitor proliferation
title_full_unstemmed PHF2-mediated H3K9me balance orchestrates heterochromatin stability and neural progenitor proliferation
title_sort PHF2-mediated H3K9me balance orchestrates heterochromatin stability and neural progenitor proliferation
dc.creator.none.fl_str_mv Aguirre Infantes, Samuel
Pappa, Stella
Padilla, Natàlia
Iacobucci, Simona
Nacht, Ana Silvina
Vicent, Guillermo P.
Jordan, Albert
Cruz, Xavier de la
Martínez-Balbás, Marian
author Aguirre Infantes, Samuel
author_facet Aguirre Infantes, Samuel
Pappa, Stella
Padilla, Natàlia
Iacobucci, Simona
Nacht, Ana Silvina
Vicent, Guillermo P.
Jordan, Albert
Cruz, Xavier de la
Martínez-Balbás, Marian
author_role author
author2 Pappa, Stella
Padilla, Natàlia
Iacobucci, Simona
Nacht, Ana Silvina
Vicent, Guillermo P.
Jordan, Albert
Cruz, Xavier de la
Martínez-Balbás, Marian
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Ministerio de Ciencia e Innovación (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv PHF2
Heterochromatin Integrity
Histone Demethylation
Neural Stem Cells
DNA damage
topic PHF2
Heterochromatin Integrity
Histone Demethylation
Neural Stem Cells
DNA damage
description Heterochromatin stability is crucial for progenitor proliferation during early neurogenesis. It relays on the maintenance of local hubs of H3K9me. However, understanding the formation of efficient localized levels of H3K9me remains limited. To address this question, we used neural stem cells to analyze the function of the H3K9me2 demethylase PHF2, which is crucial for progenitor proliferation. Through mass-spectroscopy and genome-wide assays, we show that PHF2 interacts with heterochromatin components and is enriched at pericentromeric heterochromatin (PcH) boundaries where it maintains transcriptional activity. This binding is essential for silencing the satellite repeats, preventing DNA damage and genome instability. PHF2’s depletion increases the transcription of heterochromatic repeats, accompanied by a decrease in H3K9me3 levels and alterations in PcH organization. We further show that PHF2’s PHD and catalytic domains are crucial for maintaining PcH stability, thereby safeguarding genome integrity. These results highlight the multifaceted nature of PHF2’s functions in maintaining heterochromatin stability and regulating gene expression during neural development. Our study unravels the intricate relationship between heterochromatin stability and progenitor proliferation during mammalian neurogenesis.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/372107
url http://hdl.handle.net/10261/372107
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO//BFU2015-69248-P
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-096082-B-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-125862NB-I00
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1038/s44319-024-00178-7
https://doi.org/10.1038/s44319-024-00178-7
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406591598460928
score 15.812429

Similares en LA Referencia