YAP电荷模式通过转录共缩物调解信号集成
Kirstin Meyer1,2, Klaus Yserentant2,3, Rasmi Cheloor-Kovilakam2,3
1Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
bioRxiv : the preprint server for biology
|August 16, 2024
概括
YAP和中介蛋白在干细胞中形成转录活性凝聚物. 在YAP上,特定的电荷模式,而不是净电荷,驱动这种相互作用,使适应性基因调节成为可能.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
背景情况:
- 转录因子的动态调节了基因表达.
- 生物分子凝聚物是关键的信号平台,但它们的机制尚不清楚.
- 了解YAP信号集成在转录凝聚物中的重要性至关重要.
研究的目的:
- 为了研究转录凝聚体内YAP信号集成的分子机制.
- 阐明YAP和Mediator如何共同凝结和调节基因转录.
- 揭示YAP凝结物形成在适应性基因调节反应中的作用.
主要方法:
- 在干细胞中的光片单分子成像.
- 合成冷凝物的构建和分析.
- 内在无序区域 (IDR) 序列分析和YAP的蛋白质工程.
主要成果:
- 证明了YAP和Mediator的电荷介导共冷凝成转录活性冷凝物.
- 确定了YAP的负电荷模式,而不是净电荷,对于与Mediator的正电荷块的特定相互作用至关重要.
- 观察到,转录诱导的负反会抵消YAP/Mediator的共同凝聚,从而导致适应性反应.
结论:
- 建立了YAP凝结物形成的分子框架.
- 揭示了YAP的凝聚力学促进了对动态输入的适应性转录反应.
- 提供了对YAP凝聚物的功能在新兴基因调节行为中的新见解.
相关概念视频
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
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
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
Assembly of Signaling Complexes
5.7K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.7K
Interactions Between Signaling Pathways
6.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K
Combinatorial Gene Control
8.3K
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
8.3K


