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: 7625029
• 负责人: NICHOLAS F OSBORNE
• 金额: $ 5.17万
• 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/7625029
• 关键词: Affect; Architecture; Blood Vessels; Catalytic Domain; Cell Culture Techniques; Chromatin; Chromatin Remodeling Factor; Chromatin Structure; Collaborations; Complex; Coronary Arteriosclerosis; Development; Developmental Process; Diabetes Mellitus; Disease; Embryo Loss; Embryonic Development; Endothelial Cells; Gene Expression; Genes; Genetic Transcription; Goals; Malignant Neoplasms; Mediating; Modeling; Mus; Mutation; Positioning Attribute; Postdoctoral Fellow; Process; Processed Genes; Protein Binding; Regulation; Role; 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组织水平上对基因转录进行精确调控 时间特定性。虽然长期以来人们意识到转录因子对于 调节这种特异性，越来越清楚的是，仅有转录因子不足以 控制基因表达。另一个对基因表达控制至关重要的问题是基因的结构 染色质。依赖于三磷酸腺苷的染色质重塑因子能够改变或完全改变 去除与DNA结合的蛋白质，否则会阻止转录机器的访问。这个 本项目的目标是研究PBAF(多溴相关脂肪因子)特异性SWI/SNF的功能 染色质重塑复合体亚单位BAF200在小鼠胚胎发育中的开始阐明 这个亚基在体内的重要性。此外，我收集的证据表明，SWI/SNF介导了 染色质重塑是血管生成过程中特殊需要的。因此我 建议进行实验，专门灭活内皮细胞中的BAF200，以确定它是否是PBAF？；；： 介导染色质重塑对SWI/SNF促进血管发育的作用：in‘ 此外，我建议进行实验，寻找其表达受复合体特定控制的基因 含有BAF200，在小鼠卵黄囊和内皮细胞中使用互补方法 文化模式。希望这些方法将使我能够识别参与 血管系统的发展或进一步了解已知的血管中的参与者 发育受转录调控。 因为血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是至关重要的。通过研究染色质重塑的作用 血管内皮细胞中的因子我们可能发现表达对血管重要的新基因 功能，并受染色质结构调节。这样的基因，也许还有染色质 重塑因子本身可能成为治疗血液病的有效靶点 血管受到影响，包括冠状动脉疾病、糖尿病和癌症等疾病。