Relative contributions of sex hormones, sex chromosomes, and gonads to sex differences in tissue gene regulation.
Journal
Genome research
ISSN: 1549-5469
Titre abrégé: Genome Res
Pays: United States
ID NLM: 9518021
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
07
07
2021
accepted:
29
03
2022
pubmed:
10
4
2022
medline:
18
5
2022
entrez:
9
4
2022
Statut:
ppublish
Résumé
Sex differences in physiology and disease in mammals result from the effects of three classes of factors that are inherently unequal in males and females: reversible (activational) effects of gonadal hormones, permanent (organizational) effects of gonadal hormones, and cell-autonomous effects of sex chromosomes, as well as genes driven by these classes of factors. Often, these factors act together to cause sex differences in specific phenotypes, but the relative contribution of each and the interactions among them remain unclear. Here, we used the four core genotypes (FCG) mouse model with or without hormone replacement to distinguish the effects of each class of sex-biasing factors on transcriptome regulation in liver and adipose tissues. We found that the activational hormone levels have the strongest influence on gene expression, followed by the organizational gonadal sex effect, and last, sex chromosomal effect, along with interactions among the three factors. Tissue specificity was prominent, with a major impact of estradiol on adipose tissue gene regulation and of testosterone on the liver transcriptome. The networks affected by the three sex-biasing factors include development, immunity and metabolism, and tissue-specific regulators were identified for these networks. Furthermore, the genes affected by individual sex-biasing factors and interactions among factors are associated with human disease traits such as coronary artery disease, diabetes, and inflammatory bowel disease. Our study offers a tissue-specific account of the individual and interactive contributions of major sex-biasing factors to gene regulation that have broad impact on systemic metabolic, endocrine, and immune functions.
Identifiants
pubmed: 35396276
pii: gr.275965.121
doi: 10.1101/gr.275965.121
pmc: PMC9104702
doi:
Substances chimiques
Gonadal Hormones
0
Gonadal Steroid Hormones
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
807-824Subventions
Organisme : NICHD NIH HHS
ID : R01 HD100298
Pays : United States
Organisme : NIDDK NIH HHS
ID : U54 DK120342
Pays : United States
Informations de copyright
© 2022 Blencowe et al.; Published by Cold Spring Harbor Laboratory Press.
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