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Developmental transcriptomic patterns can be altered by transgenic overexpression of Uty

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 di...

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Autores principales: Rock, Kylie D., Folts, Lillian M., Zierden, Hannah C., Marx-Rattner, Ruth, Leu, Nicolae Adrian, Nugent, Bridget M., Bale, Tracy L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687263/
https://www.ncbi.nlm.nih.gov/pubmed/38030664
http://dx.doi.org/10.1038/s41598-023-47977-x
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author Rock, Kylie D.
Folts, Lillian M.
Zierden, Hannah C.
Marx-Rattner, Ruth
Leu, Nicolae Adrian
Nugent, Bridget M.
Bale, Tracy L.
author_facet Rock, Kylie D.
Folts, Lillian M.
Zierden, Hannah C.
Marx-Rattner, Ruth
Leu, Nicolae Adrian
Nugent, Bridget M.
Bale, Tracy L.
author_sort Rock, Kylie D.
collection PubMed
description 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.
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spelling pubmed-106872632023-11-30 Developmental transcriptomic patterns can be altered by transgenic overexpression of Uty Rock, Kylie D. Folts, Lillian M. Zierden, Hannah C. Marx-Rattner, Ruth Leu, Nicolae Adrian Nugent, Bridget M. Bale, Tracy L. Sci Rep Article 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. Nature Publishing Group UK 2023-11-30 /pmc/articles/PMC10687263/ /pubmed/38030664 http://dx.doi.org/10.1038/s41598-023-47977-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Rock, Kylie D.
Folts, Lillian M.
Zierden, Hannah C.
Marx-Rattner, Ruth
Leu, Nicolae Adrian
Nugent, Bridget M.
Bale, Tracy L.
Developmental transcriptomic patterns can be altered by transgenic overexpression of Uty
title Developmental transcriptomic patterns can be altered by transgenic overexpression of Uty
title_full Developmental transcriptomic patterns can be altered by transgenic overexpression of Uty
title_fullStr Developmental transcriptomic patterns can be altered by transgenic overexpression of Uty
title_full_unstemmed Developmental transcriptomic patterns can be altered by transgenic overexpression of Uty
title_short Developmental transcriptomic patterns can be altered by transgenic overexpression of Uty
title_sort developmental transcriptomic patterns can be altered by transgenic overexpression of uty
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687263/
https://www.ncbi.nlm.nih.gov/pubmed/38030664
http://dx.doi.org/10.1038/s41598-023-47977-x
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