在单个增强剂中,两个冗余的转录因子结合点对于哺乳动物的性别确定至关重要
Meshi Ridnik1, Elisheva Abberbock1, Veronica Alipov1
1The Mina and Everard Goodman Faculty of Life Sciences and the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan 5290002, Israel.
Nucleic acids research
|March 18, 2024
概括
在Sox9基因中的基本非编码DNA.
科学领域:
- 遗传学 遗传学 是一个
- 发展生物学 发展生物学
- 哺乳动物的性别确定方法
背景情况:
- 哺乳动物中的男性发育依赖于胚胎丸中的Sry和Sox9基因.
- 删除Sox9基因的Enhancer 13 (Enh13) 会导致XY男性对女性的性别逆转.
研究的目的:
- 在Enh13中识别其功能所必需的关键元素.
- 了解丸和男性发育的分子基础.
主要方法:
- 研究了Enh13.中的转录因子结合位点 (TFBS) 中微切除的影响.
- 分析了SRY/SOX结合基因组合突变的功能后果.
主要成果:
- 在Enh13中个别的TFBS微切除没有破坏丸发育.
- 仅仅两个SRY/SOX结合基因的组合微切除取消了Enh13活性,导致XY性别逆转.
- 不同的TFBS突变导致了不同的表型结果.
结论:
- 在Enh13中,特定的核酸序列对于男性的性别确定至关重要.
- 这些非编码DNA元素的完整性对于丸正常发育至关重要.
- 在TFBS的突变变异性解释了患者的不同临床表现.
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