先驱因子Foxa2调解染色体构造变化,以激活FXR的胆汁酸点
1Department of Pharmacology, University of Virginia, Charlottesville, Virginia.
Cellular and molecular gastroenterology and hepatology
|October 25, 2023
概括
先驱因素Foxa2在肝受体激活过程中使动态色素变化成为可能. 这个过程涉及Foxa2定环,对于调节基因表达和肝脏生理学至关重要.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 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:
- 转录因子通过调节基因表达来协调肝脏生理,通常涉及远端增强剂和染色质循环.
- 先驱因子Foxa2促进核受体结合,例如Farnesoid X受体 (FXR),其缺失导致肝功能障碍 (肝内胆固醇).
研究的目的:
- 调查Foxa2在核受体的连接体激活过程中调解色素构造变化的作用,特别是FXR.
主要方法:
- 在小鼠肝脏中利用Foxa2 HiChIP (Hi-C和ChIP) 来分析Foxa2-依赖的长距离染色质相互作用.
- 用车辆控制治疗的肝脏与FXR激活剂 (GW4064) 的相互作用概况进行比较.
主要成果:
- FXR激活显著增加了全球色素相互作用和拓相关域的重新分配.
- 在FXR激动剂治疗后,Foxa2定环显著增加,表明动态染色质重塑.
- 表明在配体激活过程中额外的Foxa2结合促进了远端相互作用,并激活了目标基因表达.
结论:
- 结合体激活FXR需要全球色素结构的改变.
- 确定了Foxa2在促进这些联体诱导的染色质构造变化的新功能,扩大了它在胆酸代谢中的已知作用.
相关概念视频
Master 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
Co-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
Transducer Mechanism: Nuclear Receptors
1.4K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.4K
General Transcription Factors
5.3K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
5.3K
Transcription Factors
76.0K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
76.0K
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K


