不偏向的转录因子CRISPR屏幕确定ZNF800为肠内分泌的主要抑制剂
Lin Lin1,2,3, Jeff DeMartino2,3, Daisong Wang1,2
1Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, Netherlands.
Science (New York, N.Y.)
|October 26, 2023
概括
研究人员使用CRISPR屏幕在人体器官中确定ZNF800为肠内分泌细胞 (EEC) 差异化的关键抑制剂. 这一发现阐明了特定的转录因子如何控制肠道激素细胞的发育和代谢调节.
科学领域:
- 胃肠病学
- 细胞生物学
- 遗传学
背景情况:
- 肠内分泌细胞 (EECs) 对于新陈代谢调节,控制胰岛素,和肠道运动至关重要.
- 不同的EEC血统区分的确切机制在很大程度上是未知的.
研究的目的:
- 确定指导肠内分泌细胞分化的主要转录因子 (TF).
- 通过功能基因组学方法研究TFs在控制内分泌系承诺中的作用.
主要方法:
- 在成年人小肠器官中对所有转录因子进行了CRISPR淘汰查.
- 使用器官模型对影响细胞命运的基因进行无偏见的大规模功能查.
主要成果:
- 确定ZNF800作为内分泌系承诺的主抑制剂.
- 证明ZNF800特别限制了肠染色素细胞分化.
- 显示ZNF800直接调节一个涉及PAX4的内分泌TF网络.
结论:
- 人类器官模型能够有效地识别决定细胞命运的基因.
- 在抑制肠内分泌细胞分化方面,ZNF800起着至关重要的作用,特别是在肠内分泌细胞中.
- 了解以PAX4为中心的TF网络是解读EEC发展的关键.
相关概念视频
02:23Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
02:04Co-activators and Co-repressors
7.4K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.4K