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Developmental transcriptomic patterns can be altered by transgenic overexpression of Uty
Kylie D Rock1,2,3, Lillian M Folts1,2,4, Hannah C Zierden1,2,5
1Center for Epigenetic Research in Child Health and Brain Development, University of Maryland School of Medicine, Baltimore, USA.
Scientific Reports
|November 29, 2023
Summary
The Y-chromosome gene UTY was found to influence sex-specific development and health. Overexpressing UTY in female mice led to masculinized gene expression and altered metabolic responses, suggesting a role in sex determination and disease risk.
Area of Science:
- Genetics and Epigenetics
- Developmental Biology
- Mammalian Reproduction
Background:
- Biological sex differences are established by X and Y chromosomes.
- Epigenetic regulators on sex chromosomes, like KDM6A and DDX3X, impact phenotypic sex differences.
- The role of UTY (KDM6C), the Y-linked homolog of UTX, in developmental sex differences remains unclear.
Purpose of the Study:
- To investigate the hypothesis that UTY is a crucial transcriptional regulator during development.
- To explore UTY's potential contribution to sex-specific phenotypes and lifelong disease risks.
- To assess UTY's functional activity and impact on sex-specific outcomes.
Main Methods:
- Generated a Uty transgenic mouse model (Uty-Tg) for UTY overexpression.
- Compared transcriptomic profiles in developmental tissues, placenta, and hypothalamus of Uty-Tg females (XX + Uty) with wild-type males (XY) and females (XX).
- Conducted phenotypic examinations of adult mice to assess physiological and behavioral outcomes.
Main Results:
- UTY overexpression in female mice "masculinized" gene expression patterns in the placenta and hypothalamus.
- Gene Ontology and Gene Set Enrichment Analysis identified immune and synaptic signaling pathways associated with UTY.
- Adult Uty-expressing female mice exhibited reduced weight gain and improved glucose tolerance on a high-fat diet compared to controls.
Conclusions:
- UTY plays a functional transcriptional role in developing tissues.
- UTY has the potential to influence sex-specific developmental trajectories.
- UTY's activity may impact sex-specific health outcomes and disease susceptibility across the lifespan.
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