The Role of the PBAF-specific subunit BAF200 in blood vessel formation

PBAF特异性亚基BAF200在血管形成中的作用

• 批准号: 7435235
• 负责人: NICHOLAS F OSBORNE
• 金额: $ 4.96万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-18 至 2010-05-17
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7435235
• 关键词: Affect; Architecture; Blood Vessels; Catalytic Domain; Chromatin; Chromatin Remodeling Factor; Chromatin Structure; Class; Collaborations; Complex; Coronary Arteriosclerosis; Development; Developmental Process; Diabetes Mellitus; Disease; Embryo Loss; Embryonic Development; Endothelial Cells; Gene Expression; Genes; Genetic Transcription; Goals; Interleukin-4; Malignant Neoplasms; Mediating; Modeling; Mus; Mutation; Positioning Attribute; Postdoctoral Fellow; Process; Processed Genes; Protein Binding; Regulation; Role; Soluble Baker' s Antifol; Specificity; Tissues; Vascular System; Yolk Sac; angiogenesis; base; brahma; chromatin remodeling; in vivo; novel; polybromo; research study; transcription factor

Embryonic development requires the precise regulation of gene transcription at the levels of both tissue and temporal specificity. While it has long been appreciated that transcription factors are necessary for regulating this specificity it is becoming increasingly clear that transcription factors alone are not sufficient to control gene expression. One other issue critical to the control of gene expression is the structure of chromatin. ATP-dependent chromatin remodeling factors are capable of shifting the position of or entirely removing proteins bound to DMAthat would otherwise block the access of transcriptional machinery. The goal of this project is to examine the function of the PBAF (Polybromo Associated Fatctor) specific SWI/SNF chromatin remodeling complex subunit BAF200 in mouse embryonic development to begin to elucidated the importance of this subunit in vivo. Furthermore, evidence I have collected suggests that SWI/SNF mediated chromatin remodeling is specifically required for the process of blood vessel angiogenesis. Therefore I propose experiments to specifically inactivate BAF200 in endothelial cells to determine if it is PBAF ¿ iy,;;: mediated chromatin remodeling that is responsible for SWI/SNF contribution to vascular development: In' addition, I propose experiments to look for genes whose expression is specifically controlled by complexes containing BAF200, using complementary approaches in the mouse yolk sac and in an endothelial cell culture model. Hopefully these approaches will allow me to identify novel genes involved in the development of the vascular system or to further the understanding of how known players in vascular development are transcriptionally regulated. Because diseases of the vasculature affect so many people in the world, understanding the genes and processes involved in blood vessel development is vital. By investigating the role of chromatin remodeling factors in endothelial cells we may identify novel genes whose expression is important to blood vessel function and that are regulated by chromatin architecture. Such genes, and perhaps the chromatin remodeling factors themselves, may turn out to be effective targets for treating diseases in which blood vessels are affected, including such diseases as coronary artery disease, diabetes and cancer.

胚胎发育需要在组织和细胞水平上精确调控基因转录， 时间特异性虽然长期以来人们已经认识到转录因子是转录所必需的， 越来越清楚的是，转录因子本身不足以调节这种特异性， 控制基因表达。另一个对基因表达控制至关重要的问题是， 染色质ATP依赖性染色质重塑因子能够改变或完全改变细胞的位置， 去除与DMA结合的蛋白质，否则这些蛋白质会阻止转录机器的进入。的 本项目的目的是研究PBAF（聚溴缔合脂肪）特异性SWI/SNF的功能 染色质重塑复合物亚基BAF 200在小鼠胚胎发育中的作用得以开始阐明 这一亚基在体内的重要性。此外，我收集的证据表明，SWI/SNF介导了 染色质重塑是血管血管生成过程所特别需要的。所以我 提出实验，专门在内皮细胞中检测BAF 200，以确定它是否是PBAF。 介导的染色质重塑，负责SWI/SNF对血管发育的贡献： 此外，我还提出了一些实验来寻找其表达受复合物特异性控制的基因 含有BAF 200，在小鼠卵黄囊和内皮细胞中使用互补方法 文化模式希望这些方法能让我识别出参与这种疾病的新基因。 发展的血管系统或进一步了解如何已知的球员在血管 发育受到转录调控。 因为脉管系统疾病影响着世界上如此多的人，了解基因和 参与血管发育的过程至关重要。通过研究染色质重塑的作用 在内皮细胞中的因子，我们可以识别新的基因，其表达对血管内皮细胞是重要的， 功能，并由染色质结构调节。这样的基因，也许还有染色质 重塑因子本身，可能成为治疗疾病的有效靶标， 血管受到影响，包括冠状动脉疾病、糖尿病和癌症等疾病。