Organization of transcriptional machinery by weak multivalent interactions

通过弱多价相互作用组织转录机制

• 批准号: 10758297
• 负责人: Benjamin Sabari
• 金额: $ 2.55万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10758297
• 关键词: Biological Assay; Biological Process; Cell Differentiation process; Cell Nucleus; Cell model; Data; Defect; Development; Developmental Process; Disease; Educational process of instructing; Gene Activation; Genes; Genetic Transcription; Goals; Investigation; Mediating; Modeling; Process; Protein Region; Reporter; Role; Smooth Muscle Myocytes; Time; Transcription Coactivator; Work; functional outcomes; genomic locus; human disease; insight; myocardin; novel; parent grant; protein protein interaction; recruit

Project Summary Weak multivalent interactions mediated by intrinsically disordered regions (IDRs) of proteins have been proposed to spatially organize the transcriptional machinery into multi-component clusters, yet we know little about how these IDRs interact with specific partners to enable functional outcomes. As these interactions are highly dynamic and cluster-dependent they have been overlooked by conventional strategies to identify protein-protein interactions. Our preliminary data support our overarching hypothesis that in the context of higher-order clusters weak multivalent interactions are capable of highly specific hetero-typic interactions leading to functional organization of the nucleus. Our long-term objective is to understand how weak multivalent interactions organize specific components of the transcriptional machinery in order to enable gene activation. The objective of the parent grant is to investigate the mechanism and function of cluster-mediated interactions of IDR of found on transcriptional coactivators. The proposed work in the diversity supplement focusses on investigating myocardin (MYOCD), a smooth muscle cell specific coactivator. The proposed work is directly related to Aim 3 of the parent grant, which proposes to investigate the functional role of coactivator IDRs in various models of gene activation including reporter assays and cell models of cellular differentiation. MYOCD is a smooth muscle cell specific coactivator, and we will be investigating the role of its IDR in reporter assays and smooth muscle cell differentiation. Completion of these studies will advance the goals and objectives of the parent grant and will teach us about how the function of prevalent yet often overlooked IDRs in gene activation.

项目摘要 蛋白质内在无序区（IDR）介导的弱多价相互作用已经被提出 在空间上将转录机制组织成多组分簇，但我们对如何组织知之甚少。 这些内部发展报告与具体伙伴互动，以实现功能成果。由于这些相互作用是高度 动态和集群依赖性，他们已被忽视的传统策略，以确定蛋白质-蛋白质 交互.我们的初步数据支持我们的总体假设，即在高阶集群的背景下， 弱的多价相互作用能够产生高度特异性的异型相互作用， 核心的组织。我们的长期目标是了解弱多价相互作用是如何组织的 转录机器的特定组件，以使基因激活。的目的 本研究的目的是探讨IDR在植物中的簇介导的相互作用的机制和功能， 转录辅激活因子。多样性补充中的拟议工作集中在研究心肌素 （MYOCD），一种平滑肌细胞特异性辅激活因子。拟议的工作与母公司的目标3直接相关 格兰特，其中提出了研究功能的作用，共激活IDRs在各种模型的基因激活 包括报告基因测定和细胞分化的细胞模型。MYOCD是一种平滑肌细胞特异性 我们将研究其IDR在报告基因测定和平滑肌细胞中的作用， 分化完成这些研究将推进父母补助金的目标和宗旨， 教我们如何在基因激活中普遍但经常被忽视的IDR的功能。