Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome

Autores
Akol, Ipek; Izzo, Annalisa; Gather, Fabian; Strack, Stefanie; Heidrich, Stefanie; Óhailín, Darren; Villarreal, Alejandro; Hacker, Christine; Rauleac, Tudor; Bella, Chiara; Fischer, Andre; Manke, Thomas; Vogel, Tanja
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Forkhead box G1 (FOXG1) has important functions in neuronal differentiation and balances excitatory/inhibitory network activity. Thus far, molecular processes underlying FOXG1 function are largely unexplored. Here, we present a multiomics data set exploring how FOXG1 impacts neuronal maturation at the chromatin level in the mouse hippocampus. At a genome-wide level, FOXG1 i) both represses and activates transcription, ii) binds mainly to enhancer regions, iii) reconfigures the epigenetic landscape through bidirectional alteration of H3K27ac, H3K4me3, and chromatin accessibility, and iv) operates synergistically with NEUROD1. Interestingly, we could not detect a clear hierarchy of FOXG1 and NEUROD1, but instead, provide the evidence that they act in a highly cooperative manner to control neuronal maturation. Genes affected by the chromatin alterations impact synaptogenesis and axonogenesis. Inhibition of histone deacetylases partially rescues transcriptional alterations upon FOXG1 reduction. This integrated multiomics view of changes upon FOXG1 reduction reveals an unprecedented multimodality of FOXG1 functions converging on neuronal maturation. It fuels therapeutic options based on epigenetic drugs to alleviate, at least in part, neuronal dysfunction.
Fil: Akol, Ipek. Albert Ludwigs University of Freiburg; Alemania
Fil: Izzo, Annalisa. Albert Ludwigs University of Freiburg; Alemania
Fil: Gather, Fabian. Albert Ludwigs University of Freiburg; Alemania
Fil: Strack, Stefanie. Albert Ludwigs University of Freiburg; Alemania
Fil: Heidrich, Stefanie. Albert Ludwigs University of Freiburg; Alemania
Fil: Óhailín, Darren. Albert Ludwigs University of Freiburg; Alemania. University of Central Lancashire; Reino Unido
Fil: Villarreal, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. University of Central Lancashire; Reino Unido
Fil: Hacker, Christine. Albert Ludwigs University of Freiburg; Alemania
Fil: Rauleac, Tudor. Albert Ludwigs University of Freiburg; Alemania
Fil: Bella, Chiara. Max Planck Institute Of Immunobiology And Epigenetics; Alemania
Fil: Fischer, Andre. Universität Göttingen; Alemania. German Center for Neurodegenerative Diseases; Alemania
Fil: Manke, Thomas. Max Planck Institute Of Immunobiology And Epigenetics; Alemania
Fil: Vogel, Tanja. Albert Ludwigs University of Freiburg; Alemania
Materia
ATAC
AXONOGENESIS
HISTONE MODIFICATION
NEURONAL DIFFERENTIATION
RETT-SYNDROME
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/227905
Acceder
id CONICETDig_9be200e5e2c5826a7e7ad77f912739b9
oai_identifier_str oai:ri.conicet.gov.ar:11336/227905
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndromeAkol, IpekIzzo, AnnalisaGather, FabianStrack, StefanieHeidrich, StefanieÓhailín, DarrenVillarreal, AlejandroHacker, ChristineRauleac, TudorBella, ChiaraFischer, AndreManke, ThomasVogel, TanjaATACAXONOGENESISHISTONE MODIFICATIONNEURONAL DIFFERENTIATIONRETT-SYNDROMEhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Forkhead box G1 (FOXG1) has important functions in neuronal differentiation and balances excitatory/inhibitory network activity. Thus far, molecular processes underlying FOXG1 function are largely unexplored. Here, we present a multiomics data set exploring how FOXG1 impacts neuronal maturation at the chromatin level in the mouse hippocampus. At a genome-wide level, FOXG1 i) both represses and activates transcription, ii) binds mainly to enhancer regions, iii) reconfigures the epigenetic landscape through bidirectional alteration of H3K27ac, H3K4me3, and chromatin accessibility, and iv) operates synergistically with NEUROD1. Interestingly, we could not detect a clear hierarchy of FOXG1 and NEUROD1, but instead, provide the evidence that they act in a highly cooperative manner to control neuronal maturation. Genes affected by the chromatin alterations impact synaptogenesis and axonogenesis. Inhibition of histone deacetylases partially rescues transcriptional alterations upon FOXG1 reduction. This integrated multiomics view of changes upon FOXG1 reduction reveals an unprecedented multimodality of FOXG1 functions converging on neuronal maturation. It fuels therapeutic options based on epigenetic drugs to alleviate, at least in part, neuronal dysfunction.Fil: Akol, Ipek. Albert Ludwigs University of Freiburg; AlemaniaFil: Izzo, Annalisa. Albert Ludwigs University of Freiburg; AlemaniaFil: Gather, Fabian. Albert Ludwigs University of Freiburg; AlemaniaFil: Strack, Stefanie. Albert Ludwigs University of Freiburg; AlemaniaFil: Heidrich, Stefanie. Albert Ludwigs University of Freiburg; AlemaniaFil: Óhailín, Darren. Albert Ludwigs University of Freiburg; Alemania. University of Central Lancashire; Reino UnidoFil: Villarreal, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. University of Central Lancashire; Reino UnidoFil: Hacker, Christine. Albert Ludwigs University of Freiburg; AlemaniaFil: Rauleac, Tudor. Albert Ludwigs University of Freiburg; AlemaniaFil: Bella, Chiara. Max Planck Institute Of Immunobiology And Epigenetics; AlemaniaFil: Fischer, Andre. Universität Göttingen; Alemania. German Center for Neurodegenerative Diseases; AlemaniaFil: Manke, Thomas. Max Planck Institute Of Immunobiology And Epigenetics; AlemaniaFil: Vogel, Tanja. Albert Ludwigs University of Freiburg; AlemaniaNational Academy of Sciences2023-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/227905Akol, Ipek; Izzo, Annalisa; Gather, Fabian; Strack, Stefanie; Heidrich, Stefanie; et al.; Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 120; 2; 1-2023; 1-120027-8424CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/doi/10.1073/pnas.2122467120info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.2122467120info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:41:32Zoai:ri.conicet.gov.ar:11336/227905instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:41:33.545CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome
title Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome
spellingShingle Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome
Akol, Ipek
ATAC
AXONOGENESIS
HISTONE MODIFICATION
NEURONAL DIFFERENTIATION
RETT-SYNDROME
title_short Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome
title_full Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome
title_fullStr Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome
title_full_unstemmed Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome
title_sort Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome
dc.creator.none.fl_str_mv Akol, Ipek
Izzo, Annalisa
Gather, Fabian
Strack, Stefanie
Heidrich, Stefanie
Óhailín, Darren
Villarreal, Alejandro
Hacker, Christine
Rauleac, Tudor
Bella, Chiara
Fischer, Andre
Manke, Thomas
Vogel, Tanja
author Akol, Ipek
author_facet Akol, Ipek
Izzo, Annalisa
Gather, Fabian
Strack, Stefanie
Heidrich, Stefanie
Óhailín, Darren
Villarreal, Alejandro
Hacker, Christine
Rauleac, Tudor
Bella, Chiara
Fischer, Andre
Manke, Thomas
Vogel, Tanja
author_role author
author2 Izzo, Annalisa
Gather, Fabian
Strack, Stefanie
Heidrich, Stefanie
Óhailín, Darren
Villarreal, Alejandro
Hacker, Christine
Rauleac, Tudor
Bella, Chiara
Fischer, Andre
Manke, Thomas
Vogel, Tanja
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ATAC
AXONOGENESIS
HISTONE MODIFICATION
NEURONAL DIFFERENTIATION
RETT-SYNDROME
topic ATAC
AXONOGENESIS
HISTONE MODIFICATION
NEURONAL DIFFERENTIATION
RETT-SYNDROME
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Forkhead box G1 (FOXG1) has important functions in neuronal differentiation and balances excitatory/inhibitory network activity. Thus far, molecular processes underlying FOXG1 function are largely unexplored. Here, we present a multiomics data set exploring how FOXG1 impacts neuronal maturation at the chromatin level in the mouse hippocampus. At a genome-wide level, FOXG1 i) both represses and activates transcription, ii) binds mainly to enhancer regions, iii) reconfigures the epigenetic landscape through bidirectional alteration of H3K27ac, H3K4me3, and chromatin accessibility, and iv) operates synergistically with NEUROD1. Interestingly, we could not detect a clear hierarchy of FOXG1 and NEUROD1, but instead, provide the evidence that they act in a highly cooperative manner to control neuronal maturation. Genes affected by the chromatin alterations impact synaptogenesis and axonogenesis. Inhibition of histone deacetylases partially rescues transcriptional alterations upon FOXG1 reduction. This integrated multiomics view of changes upon FOXG1 reduction reveals an unprecedented multimodality of FOXG1 functions converging on neuronal maturation. It fuels therapeutic options based on epigenetic drugs to alleviate, at least in part, neuronal dysfunction.
Fil: Akol, Ipek. Albert Ludwigs University of Freiburg; Alemania
Fil: Izzo, Annalisa. Albert Ludwigs University of Freiburg; Alemania
Fil: Gather, Fabian. Albert Ludwigs University of Freiburg; Alemania
Fil: Strack, Stefanie. Albert Ludwigs University of Freiburg; Alemania
Fil: Heidrich, Stefanie. Albert Ludwigs University of Freiburg; Alemania
Fil: Óhailín, Darren. Albert Ludwigs University of Freiburg; Alemania. University of Central Lancashire; Reino Unido
Fil: Villarreal, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. University of Central Lancashire; Reino Unido
Fil: Hacker, Christine. Albert Ludwigs University of Freiburg; Alemania
Fil: Rauleac, Tudor. Albert Ludwigs University of Freiburg; Alemania
Fil: Bella, Chiara. Max Planck Institute Of Immunobiology And Epigenetics; Alemania
Fil: Fischer, Andre. Universität Göttingen; Alemania. German Center for Neurodegenerative Diseases; Alemania
Fil: Manke, Thomas. Max Planck Institute Of Immunobiology And Epigenetics; Alemania
Fil: Vogel, Tanja. Albert Ludwigs University of Freiburg; Alemania
description Forkhead box G1 (FOXG1) has important functions in neuronal differentiation and balances excitatory/inhibitory network activity. Thus far, molecular processes underlying FOXG1 function are largely unexplored. Here, we present a multiomics data set exploring how FOXG1 impacts neuronal maturation at the chromatin level in the mouse hippocampus. At a genome-wide level, FOXG1 i) both represses and activates transcription, ii) binds mainly to enhancer regions, iii) reconfigures the epigenetic landscape through bidirectional alteration of H3K27ac, H3K4me3, and chromatin accessibility, and iv) operates synergistically with NEUROD1. Interestingly, we could not detect a clear hierarchy of FOXG1 and NEUROD1, but instead, provide the evidence that they act in a highly cooperative manner to control neuronal maturation. Genes affected by the chromatin alterations impact synaptogenesis and axonogenesis. Inhibition of histone deacetylases partially rescues transcriptional alterations upon FOXG1 reduction. This integrated multiomics view of changes upon FOXG1 reduction reveals an unprecedented multimodality of FOXG1 functions converging on neuronal maturation. It fuels therapeutic options based on epigenetic drugs to alleviate, at least in part, neuronal dysfunction.
publishDate 2023
dc.date.none.fl_str_mv 2023-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/227905
Akol, Ipek; Izzo, Annalisa; Gather, Fabian; Strack, Stefanie; Heidrich, Stefanie; et al.; Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 120; 2; 1-2023; 1-12
0027-8424
CONICET Digital
CONICET
url http://hdl.handle.net/11336/227905
identifier_str_mv Akol, Ipek; Izzo, Annalisa; Gather, Fabian; Strack, Stefanie; Heidrich, Stefanie; et al.; Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 120; 2; 1-2023; 1-12
0027-8424
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/doi/10.1073/pnas.2122467120
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.2122467120
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844613312047742976
score 13.070432

Publicaciones similares