Developmental transcriptomic patterns can be altered by transgenic overexpression of Uty.
Developmental transcriptomic patterns can be altered by transgenic overexpression of Uty.
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DOI：
10.1038/s41598-023-47977-x
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发表时间：
2023-11-30
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
X和Y染色体上编码的遗传物质提供了建立生物性别差异的基础。在这些性染色体上表达的表观遗传调控因子，包括Kdm6a(UTX)、Kdm5c和DDX3X，对表型性别差异的转录调控具有深远的影响。虽然最近的研究支持了UTY(Kdm6c，UTX的Y连锁同源物)的功能，但它在发育性别差异中的作用尚不清楚。在这里，我们测试了这样的假设，即UTY是发育过程中重要的转录调节因子，可能有助于性别特异性表型和一生中的疾病风险。我们建立了一只随机插入的UTY转基因小鼠(UTY-TG)来过表达UTY。通过比较发育组织、胎盘和下丘脑的转录谱，我们评估了潜在的UTY功能活性，比较了表达UTY的雌性小鼠(XX + UTY)与野生型雄性(XY)和雌性(XX)小鼠。为了确定UTY的表达是否改变了生理或行为结果，对成年小鼠进行了表型检查。UTY的表达使女性基因在胎盘和下丘脑中的表达模式男性化。基因本体论(GO)和基因集丰富分析(GSEA)一致地将包括免疫和突触信号在内的通路识别为与UTY相关的生物过程。有趣的是，与提供高脂肪饮食的野生型雄性和雌性小鼠相比，表达UTY的成年雌性小鼠体重增加较少，葡萄糖耐量较高。利用UTY过表达的转基因小鼠，我们的结果为UTY在组织发育中的功能转录作用提供了新的证据，并为建立其影响性别特异性发育和健康结果的预期能力奠定了基础。
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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早期生活节目和神经发育障碍。
影响因子：
10.6
作者：
Bale, Tracy L.;Baram, Tallie Z.;Brown, Alan S.;Goldstein, Jill M.;Insel, Thomas R.;McCarthy, Margaret M.;Nemeroff, Charles B.;Reyes, Teresa M.;Simerly, Richard B.;Susser, Ezra S.;Nestler, Eric J.
通讯作者：
Nestler, Eric J.
胎盘免疫耐受性和器官移植：潜在的互连和临床意义。
影响因子：
7.3
作者：
Sun JY;Wu R;Xu J;Xue HY;Lu XJ;Ji J
通讯作者：
Ji J
DOI：
10.1038/s41568-021-00348-y
发表时间：
2021-06
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Haupt S;Caramia F;Klein SL;Rubin JB;Haupt Y
通讯作者：
Haupt Y
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.0707292104
发表时间：
2007-11-20
影响因子：
11.1
作者：
Hong, SunHwa;Cho, Young-Wook;Ge, Kai
通讯作者：
Ge, Kai