CIITA regulation of plexin-A1 in dendritic cells

CIITA 对树突状细胞中 plexin-A1 的调节

• 批准号: 6886998
• 负责人: Brian P O'Connor
• 金额: $ 3.46万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6886998
• 关键词: DNA binding protein; MHC class II antigen; T lymphocyte; cell cell interaction; chromatin immunoprecipitation; dendritic cells; gene expression; genetic promoter element; laboratory mouse; major histocompatibility complex; molecular genetics; nuclear factor kappa beta; postdoctoral investigator; small interfering RNA; transcription factor; translation factor

DESCRIPTION (provided by applicant): The MHC class II transactivator (CIITA), a master regulator of many MHC locus genes, functions as a transcriptional coactivator, associating with DNA binding proteins that influence promoter accessibility and transcription initiation. Unlike constitutively expressed transcription factors such as RFX, NF-Y and CREB, that bind MHC class II locus promoters, CIITA expression is cytokine-inducible and regulated by cell type and differentiation stage. Thus, CIITA expression in dendritic cells regulates surface levels of MHC class II receptors in response to environmental stimuli influencing the maturation state of these cells. CIITA also regulates the expression of non-MHC genes. Dendritic cells from mice deficient in CIITA do not express the semaphorin receptor, Plexin-A1 (PlexA1). PlexA1 expression regulates interactions between dendritic cells and T lymphocytes. Interestingly, PlexA1 expression is developmentally regulated in dendritic cells, perhaps through interactions of the promoter with CIITA. However, the mechanisms of CIITA regulation of PlexA1 expression have yet to be examined. The goal of this proposal is to elucidate the molecular regulation of PlexA1 expression by CIITA and the associating transcription factors in dendritic cells.

描述（由申请人提供）：MHC II 类反式激活因子（CIITA）是许多 MHC 基因座基因的主调节因子，充当转录共激活因子，与影响启动子可及性和转录起始的 DNA 结合蛋白相关联。与结合 MHC II 类基因座启动子的组成型表达转录因子（例如 RFX、NF-Y 和 CREB）不同，CIITA 表达是细胞因子诱导型，并受细胞类型和分化阶段调节。因此，树突状细胞中的 CIITA 表达调节 MHC II 类受体的表面水平，以响应影响这些细胞成熟状态的环境刺激。 CIITA 还调节非 MHC 基因的表达。 CIITA 缺陷小鼠的树突状细胞不表达信号蛋白受体 Plexin-A1 (PlexA1)。 PlexA1 表达调节树突状细胞和 T 淋巴细胞之间的相互作用。有趣的是，PlexA1 的表达在树突状细胞中受到发育调节，可能是通过启动子与 CIITA 的相互作用。然而，CIITA 调节 PlexA1 表达的机制仍有待研究。该提案的目的是阐明 CIITA 和树突状细胞中相关转录因子对 PlexA1 表达的分子调节。