人类转录介质的结构基础由其可分离的激酶模块调节
Ti-Chun Chao1, Shin-Fu Chen1, Hee Jong Kim2
1Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Molecular cell
|September 25, 2024
概括
CDK8激酶模块 (CKM) 通过阻断RNA聚合酶II向介质复合体的招募来抑制转录. 结构和功能研究揭示了CKM与中介核 (cMED) 的结合如何抑制转录启动.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 基因规则 基因规则
背景情况:
- 细胞转录媒介复合体对于基因表达至关重要.
- 它由一个核心 (cMED) 和一个调控性CDK8激酶模块 (CKM) 组成.
- CKM对cMED功能的压制机制在很大程度上是未知的.
研究的目的:
- 阐明CKM介导的cMED镇压的结构基础.
- 了解CKM如何与cMED相互作用并影响转录.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定高分辨率结构.
- 生物化学测试以确认相互作用和功能影响.
- 功能分析以评估转录活动.
主要成果:
- 获得了人类中介体和CKM的冷EM结构.
- CKM通过MED12和MED13绑定cMED,MED13的内在无序区域 (IDR) 是关键的.
- 该MED13IDR直接阻断了RNA Pol II/MED26的结合部位,从而抑制了转录.
结论:
- 这项研究为CKM介导的中介功能抑制提供了一个机制框架.
- 结构洞察力解释了CKM如何抑制RNA聚合酶II招募.
- 这项工作阐明了真核生物基因调节的一个基本方面.
关键词:
CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK9 CDK8 CDK9 CDK8 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9在CKM中,它是CKM.在CTD中,CTD是CTD.这是一个IDR IDR.在MED12中,MED12是MED12中的一个.在MED13中,MED13是MED13中的一部分.在MED26中,MED26是最重要的.在PICIC中,您可以使用PIC.的RNA聚合酶II.调解人 调解人 调解人转录 转录 是一种转录.相关概念视频
RNA Polymerase II Accessory Proteins
9.1K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.1K
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
7.3K
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...
7.3K
Cooperative Binding of Transcription Regulators
6.4K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
6.4K
Transcription Factors
75.7K
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...
75.7K
Eukaryotic Transcription Inhibitors
9.8K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.8K


