The emergence of the brain non-CpG methylation system in vertebrates

Mammalian brains feature exceptionally high levels of non-CpG DNA methylation alongside the canonical form of CpG methylation. Non-CpG methylation plays a critical regulatory role in cognitive function, which is mediated by the binding of MeCP2, the transcriptional regulator that when mutated causes...

Descripción completa

Detalles Bibliográficos
Autores: Mendoza, Alex de, Poppe, Daniel, Buckberry, Sam, Pfluege, Jahnvi, Albertin, Caroline B., Daish, Tasman, Bertrand, Stephanie, Calle-Mustienes, Elisa de la, Gómez-Skarmeta, José Luis, Nery, Joseph R., Ecker, Joseph R., Baer, Boris, Ragsdale, Clifton W., Grützner, Frank, Escrivá, Héctor, Venkatesh, Byrappa, Bogdanovic, Ozren, Lister, Ryan
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/260305
Acceso en línea:http://hdl.handle.net/10261/260305
Access Level:acceso abierto
Palabra clave:Comparative genomics
Epigenomics
Evolutionary developmental biology
Molecular evolution
id ES_a3dde2cd4d2bee65fc60ea662e9e68ce
oai_identifier_str oai:digital.csic.es:10261/260305
network_acronym_str ES
network_name_str España
repository_id_str
spelling The emergence of the brain non-CpG methylation system in vertebratesMendoza, Alex dePoppe, DanielBuckberry, SamPfluege, JahnviAlbertin, Caroline B.Daish, TasmanBertrand, StephanieCalle-Mustienes, Elisa de laGómez-Skarmeta, José LuisNery, Joseph R.Ecker, Joseph R.Baer, BorisRagsdale, Clifton W.Grützner, FrankEscrivá, HéctorVenkatesh, ByrappaBogdanovic, OzrenLister, RyanComparative genomicsEpigenomicsEvolutionary developmental biologyMolecular evolutionMammalian brains feature exceptionally high levels of non-CpG DNA methylation alongside the canonical form of CpG methylation. Non-CpG methylation plays a critical regulatory role in cognitive function, which is mediated by the binding of MeCP2, the transcriptional regulator that when mutated causes Rett syndrome. However, it is unclear whether the non-CpG neural methylation system is restricted to mammalian species with complex cognitive abilities or has deeper evolutionary origins. To test this, we investigated brain DNA methylation across 12 distantly related animal lineages, revealing that non-CpG methylation is restricted to vertebrates. We discovered that in vertebrates, non-CpG methylation is enriched within a highly conserved set of developmental genes transcriptionally repressed in adult brains, indicating that it demarcates a deeply conserved regulatory program. We also found that the writer of non-CpG methylation, DNMT3A, and the reader, MeCP2, originated at the onset of vertebrates as a result of the ancestral vertebrate whole-genome duplication. Together, we demonstrate how this novel layer of epigenetic information assembled at the root of vertebrates and gained new regulatory roles independent of the ancestral form of the canonical CpG methylation. This suggests that the emergence of non-CpG methylation may have fostered the evolution of sophisticated cognitive abilities found in the vertebrate lineage.This work was supported by the Australian Research Council (ARC) Centre of Excellence programme in Plant Energy Biology (grant no. CE140100008). R.L. was supported by a Sylvia and Charles Viertel Senior Medical Research Fellowship, ARC Future Fellowship (no. FT120100862) and Howard Hughes Medical Institute International Research Scholarship. A.d.M. was funded by an EMBO long-term fellowship (no. ALTF 144-2014). J.L.G.-S. was supported by the Spanish government (grant no. BFU2016- 74961-P) and the institutional grant Unidad de Excelencia María de Maeztu (no. MDM-2016-0687). B.V. was supported by the Biomedical Research Council of the Agency for Science, Technology and Research of Singapore. F.G. was supported by an ARC Future Fellowship (no. FT160100267). C.W.R. was supported by an NSF grant (no. IOS-1354898). J.R.E. is an investigator of the Howard Hughes Medical Institute. Genomic data was generated at the Australian Cancer Research Foundation Centre for Advanced Cancer Genomics.Springer NatureAustralian Research CouncilHoward Hughes Medical InstituteEMBOMinisterio de Economía y Competitividad (España)Agency for Science, Technology and Research A*STAR (Singapore)Australian Research CouncilAustralian Cancer Research FoundationConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220212022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/260305reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO//BFU2016-74961-Pinfo:eu-repo/grantAgreement/MINECO//MDM-2016-0687http://dx.doi.org/10.1038/s41559-020-01371-2Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2603052026-05-22T06:33:51Z
dc.title.none.fl_str_mv The emergence of the brain non-CpG methylation system in vertebrates
title The emergence of the brain non-CpG methylation system in vertebrates
spellingShingle The emergence of the brain non-CpG methylation system in vertebrates
Mendoza, Alex de
Comparative genomics
Epigenomics
Evolutionary developmental biology
Molecular evolution
title_short The emergence of the brain non-CpG methylation system in vertebrates
title_full The emergence of the brain non-CpG methylation system in vertebrates
title_fullStr The emergence of the brain non-CpG methylation system in vertebrates
title_full_unstemmed The emergence of the brain non-CpG methylation system in vertebrates
title_sort The emergence of the brain non-CpG methylation system in vertebrates
dc.creator.none.fl_str_mv Mendoza, Alex de
Poppe, Daniel
Buckberry, Sam
Pfluege, Jahnvi
Albertin, Caroline B.
Daish, Tasman
Bertrand, Stephanie
Calle-Mustienes, Elisa de la
Gómez-Skarmeta, José Luis
Nery, Joseph R.
Ecker, Joseph R.
Baer, Boris
Ragsdale, Clifton W.
Grützner, Frank
Escrivá, Héctor
Venkatesh, Byrappa
Bogdanovic, Ozren
Lister, Ryan
author Mendoza, Alex de
author_facet Mendoza, Alex de
Poppe, Daniel
Buckberry, Sam
Pfluege, Jahnvi
Albertin, Caroline B.
Daish, Tasman
Bertrand, Stephanie
Calle-Mustienes, Elisa de la
Gómez-Skarmeta, José Luis
Nery, Joseph R.
Ecker, Joseph R.
Baer, Boris
Ragsdale, Clifton W.
Grützner, Frank
Escrivá, Héctor
Venkatesh, Byrappa
Bogdanovic, Ozren
Lister, Ryan
author_role author
author2 Poppe, Daniel
Buckberry, Sam
Pfluege, Jahnvi
Albertin, Caroline B.
Daish, Tasman
Bertrand, Stephanie
Calle-Mustienes, Elisa de la
Gómez-Skarmeta, José Luis
Nery, Joseph R.
Ecker, Joseph R.
Baer, Boris
Ragsdale, Clifton W.
Grützner, Frank
Escrivá, Héctor
Venkatesh, Byrappa
Bogdanovic, Ozren
Lister, Ryan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Australian Research Council
Howard Hughes Medical Institute
EMBO
Ministerio de Economía y Competitividad (España)
Agency for Science, Technology and Research A*STAR (Singapore)
Australian Research Council
Australian Cancer Research Foundation
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Comparative genomics
Epigenomics
Evolutionary developmental biology
Molecular evolution
topic Comparative genomics
Epigenomics
Evolutionary developmental biology
Molecular evolution
description Mammalian brains feature exceptionally high levels of non-CpG DNA methylation alongside the canonical form of CpG methylation. Non-CpG methylation plays a critical regulatory role in cognitive function, which is mediated by the binding of MeCP2, the transcriptional regulator that when mutated causes Rett syndrome. However, it is unclear whether the non-CpG neural methylation system is restricted to mammalian species with complex cognitive abilities or has deeper evolutionary origins. To test this, we investigated brain DNA methylation across 12 distantly related animal lineages, revealing that non-CpG methylation is restricted to vertebrates. We discovered that in vertebrates, non-CpG methylation is enriched within a highly conserved set of developmental genes transcriptionally repressed in adult brains, indicating that it demarcates a deeply conserved regulatory program. We also found that the writer of non-CpG methylation, DNMT3A, and the reader, MeCP2, originated at the onset of vertebrates as a result of the ancestral vertebrate whole-genome duplication. Together, we demonstrate how this novel layer of epigenetic information assembled at the root of vertebrates and gained new regulatory roles independent of the ancestral form of the canonical CpG methylation. This suggests that the emergence of non-CpG methylation may have fostered the evolution of sophisticated cognitive abilities found in the vertebrate lineage.
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/260305
url http://hdl.handle.net/10261/260305
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#
info:eu-repo/grantAgreement/MINECO//BFU2016-74961-P
info:eu-repo/grantAgreement/MINECO//MDM-2016-0687
http://dx.doi.org/10.1038/s41559-020-01371-2
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
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_ 1869415433108455424
score 15,811543

Similares en LA Referencia