SWI/SNF & Yolk Sac Development

SWI/SNF

基本信息

批准号：
7575565
负责人：
TERRY R MAGNUSON
金额：
$ 37万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7575565
关键词：
ATP phosphohydrolase Actins Adopted Affect Animal Model Antibodies Apoptosis Apoptotic Binding Biological Assay Blood Blood Island Blood Vessels Blood capillaries Cell Line Cells Charge Chromatin Chromatin Structure Complementary DNA Complex Core Facility Data Defect Development Dissection Down-Regulation Embryo Endothelial Cells Enhancers Erythroid Experimental Designs Gene Expression Gene Targeting Genes Genetic Genetic Transcription Globin Goals Grant Hematopoiesis Hematopoietic Histones Human Resources In Situ In Situ Hybridization In Vitro Knock-out Lead Luciferases Measures Mediating Molecular Molecular Conformation Molecular Genetics Morphogenesis Mus Mutant Strains Mice Mutation Nucleosomes Outcome Partner in relationship Pathway interactions Phenotype Positioning Attribute Postdoctoral Fellow Probability Production Proteins Protocols documentation RNA Recruitment Activity Regulation Regulatory Element Reporter Resource Sharing Resources Role SMARCA4 gene Signal Transduction Simian virus 40 Site Small Interfering RNA Source Specificity Staging Staining method Stains T-Cell Leukemia Tail Technology Testing Time Tissues Transcription Coactivator Transcription Repressor/Corepressor Transgenes Transgenic Mice Transgenic Organisms Trees Up-Regulation Vascular remodeling WNT Signaling Pathway Work Yolk Sac angiogenesis base capillary chromatin immunoprecipitation chromatin remodeling cost in vivo interest internal control knock-down man member migration mutant novel promoter research study sperm cell tool transgene expression vasculogenesis vector

项目摘要

The mammalian yolk sac provides an important nutritive role in the early postimplantatlon embryo. Yolk sac development is highly sensitive to the regulation of temporal and spatial expression of a number of genes; however, little work has been done on the relationship of chromatin structure and the transcriptional apparatus required specifically during morphogenesis of this tissue. Transcriptional activators bound to enhancers or promoters recruit chromatin·modifying complexes, which covalently modify N-terrninal histone tails or utilize ATPase activity to alter the conformation and/or position of nucleosomes. As a result, promoters adopt an ~open" chromatin configuration so transcription can be initiated. Conversely, transcriptional repressors ean recruit similar or identical complexes to other loci to establish a ·closedchromatin configuration that precludes transcription. Existing data suggest that these complexes regulate both the hematopoietic and non·hematopoietic aspects of yolk sac development but that these functions are independent of one another. To confirm this hypothesis, a 8rg1 cDNA-transgene will be specifically expressed In the hematopoietic compartment to rescue this defect. These data will confirm whether the complexes playa distinguishable role in endothelial cells of the yolk sac. In addition, based on preliminary data, experiments are proposed to test whether down regulation of Fz5 (frizzled 5) expression and upregulation of Cdh2 (eadherin 2) on the mutant background reduces the amount of free J)·catenin for WNT signaling and that this misregulation intersects with the Tgfb pathway. Misregulation of these pathways are known to regulate proliferation, migration, differentiation and apoptosis, all of which are key steps in yolk sac development.

哺乳动物的蛋黄囊在早期置换后胚胎中提供了重要的营养作用。蛋黄的发育对调节许多基因的临时和空间表达高度敏感。但是，在该组织形态发生过程中，对染色质结构和转录设备的关系几乎没有完成。与增强子或启动子结合的转录激活剂募集染色质·修饰复合物，该复合物可将N-跨胞蛋白的尾部共价修饰或利用ATPase活性来改变核体组的组成和/或位置。 As a result, promoters adopt an ~open" chromatin configuration so transcription can be initiated. Conversely, transcriptional representations ean recruit similar or identical complexes to other local to establish a · closedchromatin configuration that precludes transcription. Existing data suggest that these complexes regulate both the hematopoietic and non-hematopoietic aspects of yolk sac development but that these functions are independent of one another. To confirm this假设，在造血室中将特别表达8RG1 cDNA - cDNA转移，以挽救这些缺陷。突变体背景减少了Wnt信号传导的游离J）·catenin的量，并且这种错误与TGFB途径相交。已知这些途径的正调会调节增殖，迁移，分化和凋亡，所有这些都是蛋黄发育的关键步骤。