TOBF1通过调节多能性基因的替代拼接来调节小鼠胚胎干细胞的命运
Meghali Aich1, Asgar Hussain Ansari1, Li Ding2
1CSIR- Institute of Genomics and Integrative Biology, New Delhi 110025, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Cell reports
|September 26, 2023
概括
长非编码RNA相关蛋白TOBF1调节小鼠胚胎干细胞 (ESC) 中的替代拼接 (AS). 这一规定对于通过控制多能性相关基因的表达来维持ESC身份至关重要.
科学领域:
- 干细胞生物学 干细胞生物学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 胚胎干细胞 (ESC) 分化成各种细胞类型.
- 转录因子和染色质修饰剂是已知的ESCs中的调节剂.
- 替代拼接 (AS) 在调节ESC基因表达中的作用仍未得到充分研究.
研究的目的:
- 研究长非编码RNA (lncRNA) 相关蛋白TOBF1在调节小鼠ESC中的替代拼接 (AS) 中的作用.
- 了解TOBF1如何为维持ESC身份做出贡献.
主要方法:
- 在老鼠ESC中,CRISPR-Cas9对TOBF1进行了淘汰.
- RNA测序用于分析基因表达和AS的全球变化.
- 染色体免疫沉测序 (ChIP-seq) 用于确定TOBF1结合位点.
- 分析了OCT-SOX结合因子及其分布.
主要成果:
- TOBF1调节了转录的AS,这对于保持鼠标ESC身份至关重要.
- 淘汰TOBF1影响了氨酸/氨酸拼接因子1 (SRSF1) 的AS.
- 改变的SRSF1 AS导致下游多能性基因的拼接和表达的全球变化.
- 确定TOBF1占用率,OCT-SOX动机和AS事件汇聚的特定核领土.
结论:
- TOBF1在调节小鼠ESC中的替代拼接方面发挥着重要作用.
- 以TOBF1为媒介的AS对于维持ESC多能性和身份至关重要.
- 该研究确定了涉及lncRNA相关蛋白质在干细胞维护中的新型调节机制.
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