发育转录基因模式可以通过Uty的转基因过度表达而改变
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
概括
发现Y染色体基因UTY会影响性别特定的发育和健康. 在雌性小鼠中过度表达UTY导致了男性化的基因表达和改变的代谢反应,这表明在性别决定和疾病风险方面发挥了作用.
科学领域:
- 遗传学和表观遗传学
- 发展生物学 发展生物学
- 哺乳动物繁殖 哺乳动物繁殖
背景情况:
- 生物性差异是由X和Y染色体建立的.
- 性染色体上的表观遗传调节者,如KDM6A和DDX3X,影响表型性差异.
- 在发育性差异中,UTY (KDM6C) 的Y链同类UTX的作用仍然不清楚.
研究的目的:
- 调查 UTY 在发育过程中是关键的转录调节器的假设.
- 探索UTY对性别特异性表型和终身疾病风险的潜在贡献.
- 评估UTY的功能活动和对性别特异性结果的影响.
主要方法:
- 为UTY过度表达生成了一个UTY转基因小鼠模型 (Uty-Tg).
- 对比了Uty-Tg雌性 (XX + Uty) 的发育组织,胎盘和下丘脑的转录组特征,与野生型雄性 (XY) 和雌性 (XX) 的转录组特征.
- 对成年小鼠进行表型检查,以评估生理和行为结果.
主要成果:
- 在雌性小鼠中UTY过度表达"男性化"了胎盘和下丘脑中的基因表达模式.
- 基因本体学和基因组丰富分析确定了与UTY相关的免疫和突触信号通路.
- 成年Uty表达性雌性小鼠在高脂肪饮食下表现出较低的体重增加和改善的葡萄糖耐受性,与对照组相比.
结论:
- UTY在发育组织中起着功能转录的作用.
- UTY有可能影响性别特定的发育轨迹.
- UTY的活动可能会影响性别特定的健康结果和整个生命周期的疾病易感性.
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