Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression.

MYC plays various roles in pluripotent stem cells, including the promotion of somatic cell reprogramming to pluripotency, the regulation of cell competition and the control of embryonic diapause. However, how Myc expression is regulated in this context remains unknown. The Myc gene lies within a ~ 3...

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Autores: Li-Bao, Lin, Díaz-Díaz, Covadonga, Raiola, Morena, Sierra, Rocío, Temiño, Susana, Moya, Francisco J, Rodriguez-Perales, Sandra, Santos, Elisa, Giovinazzo, Giovanna, Bleckwehl, Tore, Rada-Iglesias, Álvaro, Spitz, Francois, Torres, Miguel
Formato: artículo
Fecha de publicación:2024
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/19521
Acesso em linha:http://hdl.handle.net/20.500.12105/19521
Access Level:acceso abierto
Palavra-chave:Enhancer Elements, Genetic
Proto-Oncogene Proteins c-myc
Gene Expression Regulation, Developmental
Pluripotent Stem Cells
Animals
Mice
Transcription, Genetic
Embryo, Mammalian
Embryonic Stem Cells
Female
Male
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spelling Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression.Li-Bao, LinDíaz-Díaz, CovadongaRaiola, MorenaSierra, RocíoTemiño, SusanaMoya, Francisco JRodriguez-Perales, SandraSantos, ElisaGiovinazzo, GiovannaBleckwehl, ToreRada-Iglesias, ÁlvaroSpitz, FrancoisTorres, MiguelEnhancer Elements, GeneticProto-Oncogene Proteins c-mycGene Expression Regulation, DevelopmentalPluripotent Stem CellsAnimalsMiceTranscription, GeneticEmbryo, MammalianEmbryonic Stem CellsFemaleMaleMYC plays various roles in pluripotent stem cells, including the promotion of somatic cell reprogramming to pluripotency, the regulation of cell competition and the control of embryonic diapause. However, how Myc expression is regulated in this context remains unknown. The Myc gene lies within a ~ 3-megabase gene desert with multiple cis-regulatory elements. Here we use genomic rearrangements, transgenesis and targeted mutation to analyse Myc regulation in early mouse embryos and pluripotent stem cells. We identify a topologically-associated region that homes enhancers dedicated to Myc transcriptional regulation in stem cells of the pre-implantation and early post-implantation embryo. Within this region, we identify elements exclusively dedicated to Myc regulation in pluripotent cells, with distinct enhancers that sequentially activate during naive and formative pluripotency. Deletion of pluripotency-specific enhancers dampens embryonic stem cell competitive ability. These results identify a topologically defined enhancer cluster dedicated to early embryonic expression and uncover a modular mechanism for the regulation of Myc expression in different states of pluripotency.Nature Publishing GroupAgencia Estatal de Investigación (España)Unión Europea. Comisión EuropeaComunidad de Madrid (España)Instituto de Salud Carlos IIIMinisterio de Ciencia, Innovación y Universidades (España)Fundación ProCNICMinisterio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)20242024-05-2220242024-05-1020242024-05-10journal articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/19521reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme SC1-BHC07-2019open accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/195212026-06-12T12:43:37Z
dc.title.none.fl_str_mv Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression.
title Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression.
spellingShingle Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression.
Li-Bao, Lin
Enhancer Elements, Genetic
Proto-Oncogene Proteins c-myc
Gene Expression Regulation, Developmental
Pluripotent Stem Cells
Animals
Mice
Transcription, Genetic
Embryo, Mammalian
Embryonic Stem Cells
Female
Male
title_short Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression.
title_full Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression.
title_fullStr Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression.
title_full_unstemmed Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression.
title_sort Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression.
dc.creator.none.fl_str_mv Li-Bao, Lin
Díaz-Díaz, Covadonga
Raiola, Morena
Sierra, Rocío
Temiño, Susana
Moya, Francisco J
Rodriguez-Perales, Sandra
Santos, Elisa
Giovinazzo, Giovanna
Bleckwehl, Tore
Rada-Iglesias, Álvaro
Spitz, Francois
Torres, Miguel
author Li-Bao, Lin
author_facet Li-Bao, Lin
Díaz-Díaz, Covadonga
Raiola, Morena
Sierra, Rocío
Temiño, Susana
Moya, Francisco J
Rodriguez-Perales, Sandra
Santos, Elisa
Giovinazzo, Giovanna
Bleckwehl, Tore
Rada-Iglesias, Álvaro
Spitz, Francois
Torres, Miguel
author_role author
author2 Díaz-Díaz, Covadonga
Raiola, Morena
Sierra, Rocío
Temiño, Susana
Moya, Francisco J
Rodriguez-Perales, Sandra
Santos, Elisa
Giovinazzo, Giovanna
Bleckwehl, Tore
Rada-Iglesias, Álvaro
Spitz, Francois
Torres, Miguel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación (España)
Unión Europea. Comisión Europea
Comunidad de Madrid (España)
Instituto de Salud Carlos III
Ministerio de Ciencia, Innovación y Universidades (España)
Fundación ProCNIC
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
dc.subject.none.fl_str_mv Enhancer Elements, Genetic
Proto-Oncogene Proteins c-myc
Gene Expression Regulation, Developmental
Pluripotent Stem Cells
Animals
Mice
Transcription, Genetic
Embryo, Mammalian
Embryonic Stem Cells
Female
Male
topic Enhancer Elements, Genetic
Proto-Oncogene Proteins c-myc
Gene Expression Regulation, Developmental
Pluripotent Stem Cells
Animals
Mice
Transcription, Genetic
Embryo, Mammalian
Embryonic Stem Cells
Female
Male
description MYC plays various roles in pluripotent stem cells, including the promotion of somatic cell reprogramming to pluripotency, the regulation of cell competition and the control of embryonic diapause. However, how Myc expression is regulated in this context remains unknown. The Myc gene lies within a ~ 3-megabase gene desert with multiple cis-regulatory elements. Here we use genomic rearrangements, transgenesis and targeted mutation to analyse Myc regulation in early mouse embryos and pluripotent stem cells. We identify a topologically-associated region that homes enhancers dedicated to Myc transcriptional regulation in stem cells of the pre-implantation and early post-implantation embryo. Within this region, we identify elements exclusively dedicated to Myc regulation in pluripotent cells, with distinct enhancers that sequentially activate during naive and formative pluripotency. Deletion of pluripotency-specific enhancers dampens embryonic stem cell competitive ability. These results identify a topologically defined enhancer cluster dedicated to early embryonic expression and uncover a modular mechanism for the regulation of Myc expression in different states of pluripotency.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-05-22
2024
2024-05-10
2024
2024-05-10
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/19521
url http://hdl.handle.net/20.500.12105/19521
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme SC1-BHC07-2019
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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