The Role of Cysteine Rich Protein2 Binding Protein in Cardiovascular Development

富含半胱氨酸的 Protein2 结合蛋白在心血管发育中的作用

• 批准号: 7583897
• 负责人: Robert Joel Schwartz
• 金额: $ 36.63万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7583897
• 关键词: Acetylation; Animal Cap; Attenuated; Back; Binding Proteins; Bioinformatics; Boxing; CCAAT-Enhancer-Binding Protein-beta; Cardiovascular system; Cell Differentiation process; Cells; Chromatin; Chromatin Remodeling Factor; Contractile Proteins; Coupled; Cysteine; DNA Microarray Chip; Deacetylation; Development; Disease; Embryo; Embryonic Heart; Gene Expression; Gene Silencing; Gene Targeting; Generations; Genes; Genetic; Genetic Transcription; Genomics; Histone Acetylation; Histones; Knock-out; Knockout Mice; Mus; Mutant Strains Mice; Natural regeneration; Overlapping Genes; RNA Interference; Role; Signal Transduction; Smooth Muscle; Specific qualifier value; Transactivation; Transferase; Vascular Smooth Muscle; Xenopus; chromatin immunoprecipitation; chromatin remodeling; cofactor; combinatorial; embryonic stem cell; in vivo; insight; myocardin; novel; prevent; programs; promoter; public health relevance; repaired; stem

DESCRIPTION (provided by applicant): De novo activation of smooth muscle genes during the early specification of the cardiovascular system very likely requires SRF, the master regulatory platform, to form combinatorial interactions with other enriched co-factors to drive cardiovascular specified gene activity. Although SRF is indispensable for myogenic contractile protein gene expression, SRF alone is not sufficient for regulating cardiovascular cell differentiation. Previous studies implicated the involvement of chromatin acetylation-deacetylation in the control of smooth muscle gene expression. Combining bioinformatic predictions and experimental evidence, we identified a novel and important HAT that activates the nascent smooth muscle gene program. We provided multiple lines of evidence that support the concept that CSRP2BP is a novel and powerful SRF dependent Smooth Muscle Histone Acetyl-Transferase, renamed SM-HAT may be central for controlling embryonic smooth muscle gene expression and possibly vascular smooth muscle gene programs and the formation of the cardiovascular system. These studies will provide new insights in cardiovascular development and disease, and will advance strategies for regeneration and repair of the cardiovascular system. The specific aims of this project are: Specific Aim 1: To determine the function(s) of SM-HAT by gene inactivation in mice, embryonic stem (ES) cells and pro-epicardial cells. Specific Aim 2: To define the mechanisms shared between SRF and the smooth muscle enriched chromatin remodeling factor, SM-HAT Specific Aim 3: To Identify the overlapping gene networks shared between SRF and the smooth muscle enriched chromatin remodeling factor, SM-HAT PUBLIC HEALTH RELEVANCE: We identified a novel and important HAT that activates the nascent smooth muscle gene program. We provided multiple lines of evidence that support the concept that CSRP2BP is a novel and powerful SRF dependent Smooth Muscle Histone Acetyl-Transferase, renamed SM-HAT may be central for controlling embryonic smooth muscle gene expression and possibly vascular smooth muscle gene programs and the formation of the cardiovascular system. We will determine the function(s) of SM-HAT by gene inactivation in mice, embryonic stem (ES) cells and pro-epicardial cells. We will define the mechanisms shared between SRF and SM-HAT and Identify their overlapping gene networks.

描述（由申请方提供）：在心血管系统的早期特化过程中，平滑肌基因的从头激活很可能需要SRF（主调控平台）与其他富集的辅因子形成组合相互作用，以驱动心血管特定基因活性。尽管SRF对于肌源性收缩蛋白基因的表达是不可缺少的，但是单独的SRF不足以调节心血管细胞的分化。以往的研究表明，染色质乙酰化-去乙酰化参与了平滑肌基因表达的调控。结合生物信息学预测和实验证据，我们确定了一种新的和重要的HAT，激活新生平滑肌基因程序。我们提供了多条证据支持CSRP 2BP是一种新的和强大的SRF依赖性平滑肌组蛋白乙酰转移酶的概念，更名为SM-HAT可能是控制胚胎平滑肌基因表达和可能的血管平滑肌基因程序和心血管系统形成的核心。这些研究将为心血管发育和疾病提供新的见解，并将推进心血管系统再生和修复的策略。本项目的具体目标是：具体目标1：通过小鼠、胚胎干（ES）细胞和前心外膜细胞中的基因失活来确定SM-HAT的功能。具体目标二：为了确定SRF和平滑肌富集染色质重塑因子之间共享的机制，SM-HAT特定目标3：为了确定SRF和平滑肌富集染色质重塑因子之间共享的重叠基因网络，SM-HAT公共卫生相关性：我们确定了一种新的重要的HAT，它激活了新生的平滑肌基因程序。我们提供了多条证据支持CSRP 2BP是一种新的和强大的SRF依赖性平滑肌组蛋白乙酰转移酶的概念，更名为SM-HAT可能是控制胚胎平滑肌基因表达和可能的血管平滑肌基因程序和心血管系统形成的核心。我们将通过小鼠、胚胎干细胞和原心外膜细胞中的基因失活来确定SM-HAT的功能。我们将定义SRF和SM-HAT之间共享的机制，并确定它们的重叠基因网络。