Developmental changes and sex differences in DNA methylation and demethylation in hypothalamic regions of the mouse brain

Autores
Cisternas, Carla Daniela; Cortes, Laura R.; Bruggeman, Emily C.; Yao, Bing; Forger, Nancy G.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
DNA methylation is dynamically modulated during postnatal brain development, and plays a key role in neuronal lineage commitment. This epigenetic mark has also recently been implicated in the development of neural sex differences, many of which are found in the hypothalamus. The level of DNA methylation depends on a balance between the placement of methyl marks by DNA methyltransferases (Dnmts) and their removal, which is catalyzed by ten-eleven translocation (Tet) methylcytosine dioxygenases. Here, we examined developmental changes and sex differences in the expression of Tet and Dnmt enzymes from birth to adulthood in two hypothalamic regions (the preoptic area and ventromedial nucleus) and the hippocampus of mice. We found highest expression of all Tet enzymes (Tet1, Tet2, Tet3) and Dnmts (Dnmt1, Dnmt3a, Dnmt3b) in newborns, despite the fact that global methylation and hydroxymethylation were at their lowest levels at birth. Expression of the Dnmt co-activator, Dnmt3l, followed a pattern opposite to that of the canonical Dnmts (i.e., was very low in newborns and increased with age). Tet enzyme activity was much higher at birth than at weaning in both the hypothalamus and hippocampus, mirroring developmental changes in gene expression. Sex differences in Tet enzyme expression were seen in all brain regions examined during the first week of life, whereas Dnmt expression was more balanced between the sexes. Neonatal testosterone treatment of females only partially masculinized enzyme expression. Thus, Tet expression and activity are elevated during neonatal brain development, and may play important roles in sexual differentiation of the brain.
Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Georgia State University; Estados Unidos
Fil: Cortes, Laura R.. Georgia State University; Estados Unidos
Fil: Bruggeman, Emily C.. Emory University School Of Medicine; Estados Unidos
Fil: Yao, Bing. Emory University School Of Medicine; Estados Unidos
Fil: Forger, Nancy G.. Georgia State University; Estados Unidos
Materia
5-HYDROXYMETHYLCYTOSINE
5-METHYLCYTOSINE
DNA HYDROXYMETHYLATION
DNA METHYLATION
DNA METHYLTRANSFERASES
HIPPOCAMPUS
HYPOTHALAMUS
TET METHYLCYTOSINE DIOXYGENASES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/140248

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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Developmental changes and sex differences in DNA methylation and demethylation in hypothalamic regions of the mouse brainCisternas, Carla DanielaCortes, Laura R.Bruggeman, Emily C.Yao, BingForger, Nancy G.5-HYDROXYMETHYLCYTOSINE5-METHYLCYTOSINEDNA HYDROXYMETHYLATIONDNA METHYLATIONDNA METHYLTRANSFERASESHIPPOCAMPUSHYPOTHALAMUSTET METHYLCYTOSINE DIOXYGENASEShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3DNA methylation is dynamically modulated during postnatal brain development, and plays a key role in neuronal lineage commitment. This epigenetic mark has also recently been implicated in the development of neural sex differences, many of which are found in the hypothalamus. The level of DNA methylation depends on a balance between the placement of methyl marks by DNA methyltransferases (Dnmts) and their removal, which is catalyzed by ten-eleven translocation (Tet) methylcytosine dioxygenases. Here, we examined developmental changes and sex differences in the expression of Tet and Dnmt enzymes from birth to adulthood in two hypothalamic regions (the preoptic area and ventromedial nucleus) and the hippocampus of mice. We found highest expression of all Tet enzymes (Tet1, Tet2, Tet3) and Dnmts (Dnmt1, Dnmt3a, Dnmt3b) in newborns, despite the fact that global methylation and hydroxymethylation were at their lowest levels at birth. Expression of the Dnmt co-activator, Dnmt3l, followed a pattern opposite to that of the canonical Dnmts (i.e., was very low in newborns and increased with age). Tet enzyme activity was much higher at birth than at weaning in both the hypothalamus and hippocampus, mirroring developmental changes in gene expression. Sex differences in Tet enzyme expression were seen in all brain regions examined during the first week of life, whereas Dnmt expression was more balanced between the sexes. Neonatal testosterone treatment of females only partially masculinized enzyme expression. Thus, Tet expression and activity are elevated during neonatal brain development, and may play important roles in sexual differentiation of the brain.Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Georgia State University; Estados UnidosFil: Cortes, Laura R.. Georgia State University; Estados UnidosFil: Bruggeman, Emily C.. Emory University School Of Medicine; Estados UnidosFil: Yao, Bing. Emory University School Of Medicine; Estados UnidosFil: Forger, Nancy G.. Georgia State University; Estados UnidosLandes Bioscience2019-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/140248Cisternas, Carla Daniela; Cortes, Laura R.; Bruggeman, Emily C.; Yao, Bing; Forger, Nancy G.; Developmental changes and sex differences in DNA methylation and demethylation in hypothalamic regions of the mouse brain; Landes Bioscience; Epigenetics; 15; 1-2; 8-2019; 72-841559-2294CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1080/15592294.2019.1649528info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/15592294.2019.1649528info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:17:09Zoai:ri.conicet.gov.ar:11336/140248instacron: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 10:17:10.235CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Developmental changes and sex differences in DNA methylation and demethylation in hypothalamic regions of the mouse brain
title Developmental changes and sex differences in DNA methylation and demethylation in hypothalamic regions of the mouse brain
spellingShingle Developmental changes and sex differences in DNA methylation and demethylation in hypothalamic regions of the mouse brain
Cisternas, Carla Daniela
5-HYDROXYMETHYLCYTOSINE
5-METHYLCYTOSINE
DNA HYDROXYMETHYLATION
DNA METHYLATION
DNA METHYLTRANSFERASES
HIPPOCAMPUS
HYPOTHALAMUS
TET METHYLCYTOSINE DIOXYGENASES
title_short Developmental changes and sex differences in DNA methylation and demethylation in hypothalamic regions of the mouse brain
title_full Developmental changes and sex differences in DNA methylation and demethylation in hypothalamic regions of the mouse brain
title_fullStr Developmental changes and sex differences in DNA methylation and demethylation in hypothalamic regions of the mouse brain
title_full_unstemmed Developmental changes and sex differences in DNA methylation and demethylation in hypothalamic regions of the mouse brain
title_sort Developmental changes and sex differences in DNA methylation and demethylation in hypothalamic regions of the mouse brain
dc.creator.none.fl_str_mv Cisternas, Carla Daniela
Cortes, Laura R.
Bruggeman, Emily C.
Yao, Bing
Forger, Nancy G.
author Cisternas, Carla Daniela
author_facet Cisternas, Carla Daniela
Cortes, Laura R.
Bruggeman, Emily C.
Yao, Bing
Forger, Nancy G.
author_role author
author2 Cortes, Laura R.
Bruggeman, Emily C.
Yao, Bing
Forger, Nancy G.
author2_role author
author
author
author
dc.subject.none.fl_str_mv 5-HYDROXYMETHYLCYTOSINE
5-METHYLCYTOSINE
DNA HYDROXYMETHYLATION
DNA METHYLATION
DNA METHYLTRANSFERASES
HIPPOCAMPUS
HYPOTHALAMUS
TET METHYLCYTOSINE DIOXYGENASES
topic 5-HYDROXYMETHYLCYTOSINE
5-METHYLCYTOSINE
DNA HYDROXYMETHYLATION
DNA METHYLATION
DNA METHYLTRANSFERASES
HIPPOCAMPUS
HYPOTHALAMUS
TET METHYLCYTOSINE DIOXYGENASES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv DNA methylation is dynamically modulated during postnatal brain development, and plays a key role in neuronal lineage commitment. This epigenetic mark has also recently been implicated in the development of neural sex differences, many of which are found in the hypothalamus. The level of DNA methylation depends on a balance between the placement of methyl marks by DNA methyltransferases (Dnmts) and their removal, which is catalyzed by ten-eleven translocation (Tet) methylcytosine dioxygenases. Here, we examined developmental changes and sex differences in the expression of Tet and Dnmt enzymes from birth to adulthood in two hypothalamic regions (the preoptic area and ventromedial nucleus) and the hippocampus of mice. We found highest expression of all Tet enzymes (Tet1, Tet2, Tet3) and Dnmts (Dnmt1, Dnmt3a, Dnmt3b) in newborns, despite the fact that global methylation and hydroxymethylation were at their lowest levels at birth. Expression of the Dnmt co-activator, Dnmt3l, followed a pattern opposite to that of the canonical Dnmts (i.e., was very low in newborns and increased with age). Tet enzyme activity was much higher at birth than at weaning in both the hypothalamus and hippocampus, mirroring developmental changes in gene expression. Sex differences in Tet enzyme expression were seen in all brain regions examined during the first week of life, whereas Dnmt expression was more balanced between the sexes. Neonatal testosterone treatment of females only partially masculinized enzyme expression. Thus, Tet expression and activity are elevated during neonatal brain development, and may play important roles in sexual differentiation of the brain.
Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Georgia State University; Estados Unidos
Fil: Cortes, Laura R.. Georgia State University; Estados Unidos
Fil: Bruggeman, Emily C.. Emory University School Of Medicine; Estados Unidos
Fil: Yao, Bing. Emory University School Of Medicine; Estados Unidos
Fil: Forger, Nancy G.. Georgia State University; Estados Unidos
description DNA methylation is dynamically modulated during postnatal brain development, and plays a key role in neuronal lineage commitment. This epigenetic mark has also recently been implicated in the development of neural sex differences, many of which are found in the hypothalamus. The level of DNA methylation depends on a balance between the placement of methyl marks by DNA methyltransferases (Dnmts) and their removal, which is catalyzed by ten-eleven translocation (Tet) methylcytosine dioxygenases. Here, we examined developmental changes and sex differences in the expression of Tet and Dnmt enzymes from birth to adulthood in two hypothalamic regions (the preoptic area and ventromedial nucleus) and the hippocampus of mice. We found highest expression of all Tet enzymes (Tet1, Tet2, Tet3) and Dnmts (Dnmt1, Dnmt3a, Dnmt3b) in newborns, despite the fact that global methylation and hydroxymethylation were at their lowest levels at birth. Expression of the Dnmt co-activator, Dnmt3l, followed a pattern opposite to that of the canonical Dnmts (i.e., was very low in newborns and increased with age). Tet enzyme activity was much higher at birth than at weaning in both the hypothalamus and hippocampus, mirroring developmental changes in gene expression. Sex differences in Tet enzyme expression were seen in all brain regions examined during the first week of life, whereas Dnmt expression was more balanced between the sexes. Neonatal testosterone treatment of females only partially masculinized enzyme expression. Thus, Tet expression and activity are elevated during neonatal brain development, and may play important roles in sexual differentiation of the brain.
publishDate 2019
dc.date.none.fl_str_mv 2019-08
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/11336/140248
Cisternas, Carla Daniela; Cortes, Laura R.; Bruggeman, Emily C.; Yao, Bing; Forger, Nancy G.; Developmental changes and sex differences in DNA methylation and demethylation in hypothalamic regions of the mouse brain; Landes Bioscience; Epigenetics; 15; 1-2; 8-2019; 72-84
1559-2294
CONICET Digital
CONICET
url http://hdl.handle.net/11336/140248
identifier_str_mv Cisternas, Carla Daniela; Cortes, Laura R.; Bruggeman, Emily C.; Yao, Bing; Forger, Nancy G.; Developmental changes and sex differences in DNA methylation and demethylation in hypothalamic regions of the mouse brain; Landes Bioscience; Epigenetics; 15; 1-2; 8-2019; 72-84
1559-2294
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1080/15592294.2019.1649528
info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/15592294.2019.1649528
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Landes Bioscience
publisher.none.fl_str_mv Landes Bioscience
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
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