Developmental transcriptomic patterns can be altered by transgenic overexpression of Uty.

Male Female Animals Mice Transcriptome Prospective Studies Gene Expression Regulation Gene Expression Profiling Mice, Transgenic

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
30 Nov 2023
Historique:
received: 12 05 2023
accepted: 20 11 2023
medline: 1 12 2023
pubmed: 30 11 2023
entrez: 29 11 2023
Statut: epublish

Résumé

The genetic material encoded on X and Y chromosomes provides the foundation by which biological sex differences are established. Epigenetic regulators expressed on these sex chromosomes, including Kdm6a (Utx), Kdm5c, and Ddx3x have far-reaching impacts on transcriptional control of phenotypic sex differences. Although the functionality of UTY (Kdm6c, the Y-linked homologue of UTX), has been supported by more recent studies, its role in developmental sex differences is not understood. Here we test the hypothesis that UTY is an important transcriptional regulator during development that could contribute to sex-specific phenotypes and disease risks across the lifespan. We generated a random insertion Uty transgenic mouse (Uty-Tg) to overexpress Uty. By comparing transcriptomic profiles in developmental tissues, placenta and hypothalamus, we assessed potential UTY functional activity, comparing Uty-expressing female mice (XX + Uty) with wild-type male (XY) and female (XX) mice. To determine if Uty expression altered physiological or behavioral outcomes, adult mice were phenotypically examined. Uty expression masculinized female gene expression patterns in both the placenta and hypothalamus. Gene ontology (GO) and gene set enrichment analysis (GSEA) consistently identified pathways including immune and synaptic signaling as biological processes associated with UTY. Interestingly, adult females expressing Uty gained less weight and had a greater glucose tolerance compared to wild-type male and female mice when provided a high-fat diet. Utilizing a Uty-overexpressing transgenic mouse, our results provide novel evidence as to a functional transcriptional role for UTY in developing tissues, and a foundation to build on its prospective capacity to influence sex-specific developmental and health outcomes.

Identifiants

DOI: 10.1038/s41598-023-47977-x PMID: 38030664 PMC: PMC10687263
pubmed: 38030664
doi: 10.1038/s41598-023-47977-x
pii: 10.1038/s41598-023-47977-x
pmc: PMC10687263
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

21082

Subventions

Organisme : National Institute of Child Health and Human Development
ID : R01HD097093

Informations de copyright

© 2023. The Author(s).

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Auteurs

Kylie D Rock (KD)

Center for Epigenetic Research in Child Health and Brain Development, University of Maryland School of Medicine, Baltimore, USA.
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Department of Biological Sciences, Clemson University, Clemson, SC, 29634, USA.

Lillian M Folts (LM)

Center for Epigenetic Research in Child Health and Brain Development, University of Maryland School of Medicine, Baltimore, USA.
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Biomedical Sciences Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.

Hannah C Zierden (HC)

Center for Epigenetic Research in Child Health and Brain Development, University of Maryland School of Medicine, Baltimore, USA.
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, MD, 20740, USA.

Ruth Marx-Rattner (R)

Center for Epigenetic Research in Child Health and Brain Development, University of Maryland School of Medicine, Baltimore, USA.
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

Nicolae Adrian Leu (NA)

Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Bridget M Nugent (BM)

Center for Epigenetic Research in Child Health and Brain Development, University of Maryland School of Medicine, Baltimore, USA.
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

Tracy L Bale (TL)

Center for Epigenetic Research in Child Health and Brain Development, University of Maryland School of Medicine, Baltimore, USA. Tracy.Bale@cuanschutz.edu.
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. Tracy.Bale@cuanschutz.edu.
University of Colorado School of Medicine, CU Anschutz Medical Campus, 12800 E. 19th Avenue, Aurora, CO, 80045, USA. Tracy.Bale@cuanschutz.edu.
Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. Tracy.Bale@cuanschutz.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Developmental transcriptomic patterns can be...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Developmental transcriptomic patterns can be...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Developmental transcriptomic patterns can be...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Developmental transcriptomic patterns can be...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Developmental transcriptomic patterns can be...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Developmental transcriptomic patterns can be...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Developmental transcriptomic patterns can be...