在促进器和增强器上结合NMNAT1配对NAD合成到RNA聚合酶II参与
bioRxiv : the preprint server for biology
|July 14, 2025
概括
尼古丁胺胺氨基二核酸 (NAD+) 生产酶NMNAT1直接调节基因转录. NMNAT1结合活跃的基因区域,影响RNA聚合酶II进行DNA复制和细胞周期控制.
科学领域:
- 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.
- 代谢调节 代谢调节 代谢调节
背景情况:
- 基因表达依赖于动态染色质修饰,受NAD+等代谢物影响.
- 缺少NAD+与癌症,代谢障碍和衰老有关,强调需要调节NAD+的生产.
- 核NAD+合成酶NMNAT1支持染色质修饰剂,但其在转录中的直接作用尚不清楚.
研究的目的:
- 研究NMNAT1在转录调节中的全基因组调节功能.
- 阐明NMNAT1在将NAD+代谢与基因表达联系中的作用.
主要方法:
- 综合的多omics分析,包括RNA测序 (RNA-seq) 和CUT&Tag.
- 对NMNAT1结合部位的全基因组分析.
- 对NMNAT1淘汰细胞的分析,以评估对基因表达和RNA聚合酶II占用量的影响.
主要成果:
- NMNAT1与参与DNA复制,细胞循环和染色质调节的活跃转录基因的促进剂和增强剂结合.
- NMNAT1淘汰导致RNA聚合酶II在下调基因中的占用率降低.
- 通过RNA聚合酶II的参与,NMNAT1参与了转录激活.
结论:
- NMNAT1在基因特异性转录调节中发挥着直接作用.
- NMNAT1在局部NAD+生产和基因表达的控制之间起到至关重要的作用.
- 这些发现为转录的代谢调节及其对细胞过程的影响提供了新的见解.
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