Cell consequences of loss of function of the epigenetic factor EHMT1

EHMT1 is an epigenetic factor with histone methyltransferase activity that appears mutated in Kleefstra syndrome, a neurodevelopmental genetic disorder characterized by developmental delay, intellectual disability, and autistic-like features. Despite recent progress in the study of the function of t...

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Detalhes bibliográficos
Autores: Iglesias Ortega, Lucía, Megías Fernández, Clara, Domínguez Giménez, Paloma, Jimeno González, Silvia, Rivero Canalejo, Sabrina
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/147386
Acesso em linha:https://hdl.handle.net/11441/147386
https://doi.org/10.1016/j.cellsig.2023.110734
Access Level:acceso abierto
Palavra-chave:Cell biology
EHMT1
Epigenetics
Kleefstra syndrome
Neurodevelopment
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spelling Cell consequences of loss of function of the epigenetic factor EHMT1Iglesias Ortega, LucíaMegías Fernández, ClaraDomínguez Giménez, PalomaJimeno González, SilviaRivero Canalejo, SabrinaCell biologyEHMT1EpigeneticsKleefstra syndromeNeurodevelopmentEHMT1 is an epigenetic factor with histone methyltransferase activity that appears mutated in Kleefstra syndrome, a neurodevelopmental genetic disorder characterized by developmental delay, intellectual disability, and autistic-like features. Despite recent progress in the study of the function of this gene and the molecular etiology of the disease, our knowledge of how EHMT1 haploinsufficiency causes Kleefstra syndrome is still very limited. Here, we show that EHMT1 depletion in RPE1 cells leads to alterations in the morphology and distribution of different subcellular structures, such as the Golgi apparatus, the lysosomes and different cell adhesion components. EHMT1 downregulation also increases centriolar satellites detection, which may indicate a role for EHMT1 in centrosome functioning. Furthermore, the migration process is also altered in EHMT1 depleted cells, which show reduced migration capacity. We consider that the described phenotypes could open new possibilities for understanding the functional impact of EHMT1 haploinsufficiency in Kleefstra syndrome, helping to elucidate the link between epigenetic regulation and the underlying cellular mechanisms that result in this neurodevelopmental disorder. This knowledge could be relevant not only for the treatment of this syndrome, but also for other neurodevelopmental conditions that could share similar deregulated cellular pathways.ElsevierGenéticaCitología e Histología Normal y Patológica2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/147386https://doi.org/10.1016/j.cellsig.2023.110734reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésCellular Signalling, 108, 110734.https://doi.org/10.1016/j.cellsig.2023.110734info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1473862026-06-17T12:51:07Z
dc.title.none.fl_str_mv Cell consequences of loss of function of the epigenetic factor EHMT1
title Cell consequences of loss of function of the epigenetic factor EHMT1
spellingShingle Cell consequences of loss of function of the epigenetic factor EHMT1
Iglesias Ortega, Lucía
Cell biology
EHMT1
Epigenetics
Kleefstra syndrome
Neurodevelopment
title_short Cell consequences of loss of function of the epigenetic factor EHMT1
title_full Cell consequences of loss of function of the epigenetic factor EHMT1
title_fullStr Cell consequences of loss of function of the epigenetic factor EHMT1
title_full_unstemmed Cell consequences of loss of function of the epigenetic factor EHMT1
title_sort Cell consequences of loss of function of the epigenetic factor EHMT1
dc.creator.none.fl_str_mv Iglesias Ortega, Lucía
Megías Fernández, Clara
Domínguez Giménez, Paloma
Jimeno González, Silvia
Rivero Canalejo, Sabrina
author Iglesias Ortega, Lucía
author_facet Iglesias Ortega, Lucía
Megías Fernández, Clara
Domínguez Giménez, Paloma
Jimeno González, Silvia
Rivero Canalejo, Sabrina
author_role author
author2 Megías Fernández, Clara
Domínguez Giménez, Paloma
Jimeno González, Silvia
Rivero Canalejo, Sabrina
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Genética
Citología e Histología Normal y Patológica
dc.subject.none.fl_str_mv Cell biology
EHMT1
Epigenetics
Kleefstra syndrome
Neurodevelopment
topic Cell biology
EHMT1
Epigenetics
Kleefstra syndrome
Neurodevelopment
description EHMT1 is an epigenetic factor with histone methyltransferase activity that appears mutated in Kleefstra syndrome, a neurodevelopmental genetic disorder characterized by developmental delay, intellectual disability, and autistic-like features. Despite recent progress in the study of the function of this gene and the molecular etiology of the disease, our knowledge of how EHMT1 haploinsufficiency causes Kleefstra syndrome is still very limited. Here, we show that EHMT1 depletion in RPE1 cells leads to alterations in the morphology and distribution of different subcellular structures, such as the Golgi apparatus, the lysosomes and different cell adhesion components. EHMT1 downregulation also increases centriolar satellites detection, which may indicate a role for EHMT1 in centrosome functioning. Furthermore, the migration process is also altered in EHMT1 depleted cells, which show reduced migration capacity. We consider that the described phenotypes could open new possibilities for understanding the functional impact of EHMT1 haploinsufficiency in Kleefstra syndrome, helping to elucidate the link between epigenetic regulation and the underlying cellular mechanisms that result in this neurodevelopmental disorder. This knowledge could be relevant not only for the treatment of this syndrome, but also for other neurodevelopmental conditions that could share similar deregulated cellular pathways.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/147386
https://doi.org/10.1016/j.cellsig.2023.110734
url https://hdl.handle.net/11441/147386
https://doi.org/10.1016/j.cellsig.2023.110734
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cellular Signalling, 108, 110734.
https://doi.org/10.1016/j.cellsig.2023.110734
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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