Sex differences in gene expression of X-linked histone demethylase Kdm6a in embryonic hypothalamic neurons

Kdm6a and Kdm5c are histone demethylases that play an important role as epigenetic regulators of gene transcription by removing the di- and tri-methylation of Lys27 or Lys4 on histone H3 (H3K27me2/me3 - H3K4me2/me3). Both demethylases are implicated in regulation of transcription during neuronal gro...

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Autores principales: Cabrera Zapata, Lucas Ezequiel, Sosa, Camila, Cambiasso, María Julia
Formato: conferenceObject
Lenguaje:Inglés
Publicado: 2022
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Acceso en línea:http://hdl.handle.net/11086/24543
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id I10-R14111086-24543
record_format dspace
institution Universidad Nacional de Córdoba
institution_str I-10
repository_str R-141
collection Repositorio Digital Universitario (UNC)
language Inglés
topic Genes, X-Linked
Genes Ligados a X
Histone demethylase
Histona demetilasas
Estradiol
Caracteres sexuales
Sex characteristics
spellingShingle Genes, X-Linked
Genes Ligados a X
Histone demethylase
Histona demetilasas
Estradiol
Caracteres sexuales
Sex characteristics
Cabrera Zapata, Lucas Ezequiel
Sosa, Camila
Cambiasso, María Julia
Sex differences in gene expression of X-linked histone demethylase Kdm6a in embryonic hypothalamic neurons
topic_facet Genes, X-Linked
Genes Ligados a X
Histone demethylase
Histona demetilasas
Estradiol
Caracteres sexuales
Sex characteristics
description Kdm6a and Kdm5c are histone demethylases that play an important role as epigenetic regulators of gene transcription by removing the di- and tri-methylation of Lys27 or Lys4 on histone H3 (H3K27me2/me3 - H3K4me2/me3). Both demethylases are implicated in regulation of transcription during neuronal growth and differentiation, being possible to hypothesize that they may contribute to generate sex differences in brain since they are encoded by X-linked genes and escape X-chromosome inactivation. Using the Four Core Genotypes (FCG) mouse model, we first analyzed the expression of Kdm6a and Kdm5c genes by RT-qPCR in primary hypothalamic neuron cultures from E15. Only Kdm6a showed differences between genotypes, presenting higher levels of expression in XX than in XY neurons (p<0.05), regardless of the embryo sex. Estradiol 10-10 M did not affect such expression pattern in vitro. When we measured Kdm6a mRNA in the ventromedial hypothalamic region of adults, we found only XX males presented higher levels than the other three genotypes. We next evaluated the effect of Kdm6a/b activity inhibitor GSK-J4 on the sexually dimorphic expression of neurogenin 3 (Ngn3), a gene involved in the neuritogenesis of cultured hypothalamic neurons. Our preliminary results showed that GSK-J4 diminishes Ngn3 expression only in male cultures. Further experiments are required to better understand the role of Kdm6a in generation of sex differences in growth and differentiation of hypothalamic neurons. Financial support: CONICET, ANPCyT and SECyT-UNC, Argentina.
format conferenceObject
author Cabrera Zapata, Lucas Ezequiel
Sosa, Camila
Cambiasso, María Julia
author_facet Cabrera Zapata, Lucas Ezequiel
Sosa, Camila
Cambiasso, María Julia
author_sort Cabrera Zapata, Lucas Ezequiel
title Sex differences in gene expression of X-linked histone demethylase Kdm6a in embryonic hypothalamic neurons
title_short Sex differences in gene expression of X-linked histone demethylase Kdm6a in embryonic hypothalamic neurons
title_full Sex differences in gene expression of X-linked histone demethylase Kdm6a in embryonic hypothalamic neurons
title_fullStr Sex differences in gene expression of X-linked histone demethylase Kdm6a in embryonic hypothalamic neurons
title_full_unstemmed Sex differences in gene expression of X-linked histone demethylase Kdm6a in embryonic hypothalamic neurons
title_sort sex differences in gene expression of x-linked histone demethylase kdm6a in embryonic hypothalamic neurons
publishDate 2022
url http://hdl.handle.net/11086/24543
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