EARLY GENE EXPRESSION DURING T CELL ACTIVATION

T 细胞激活期间的早期基因表达

• 批准号: 7381289
• 负责人: PATRICK E FIELDS
• 金额: $ 4.46万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-27 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381289
• 关键词: cell differentiation; chromatin; cytokine; gene expression

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Appropriate T cell differentiation is a critical component of a normal immune response and insures sufficient immunity to a variety of insults, including microbial pathogens. During T cell differentiation, the cytokine loci undergo significant changes in chromatin structure that facilitate coordinated expression of the cytokine genes. We recently found that altered histone acetylation, coupled with cytokine gene transcription, occur within hours of T cell stimulation. Interestingly, the patterns of transcription and chromatin remodeling were independent of Th1/Th2 polarization. The early changes in histone modifications at the promoters of the cytokine loci were plasic and could be maintained or reversed depending on the cytokine environment that the T cells encountered subsequently. The goal of this proposal is to examine early cytokine transcription as well as changes in the local chromatin environment around the cytokine loci to determine whether these early changes set the stage for subsequent effector differentiation and thus may be an important determinant of cell fate. The scientific aims of this proposal are to study the regulation of early transcription of T helper cytokines in uncommitted T cells. We hypothesize that this early transcription is a critical step in determining the ultimate differentiated state of the effector cells. We will assess the role of chromatin remodeling within the cytokine loci on this early transcription and compare these events to those in differentiated effector cells. Inappropriate T cell differentiation has been implicated in a number of pathological states and is a critical determinant of immune responsiveness.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。适当的T细胞分化是正常免疫应答的关键组成部分，并确保对各种损伤（包括微生物病原体）的足够免疫力。在T细胞分化期间，细胞因子基因座经历染色质结构的显著变化，其促进细胞因子基因的协调表达。我们最近发现，改变组蛋白乙酰化，加上细胞因子基因转录，发生在T细胞刺激的几个小时内。有趣的是，转录和染色质重塑的模式是独立的Th 1/Th 2极化。细胞因子基因座启动子处组蛋白修饰的早期变化是可塑的，并且可以根据T细胞随后遇到的细胞因子环境来维持或逆转。该建议的目的是检查早期细胞因子转录以及细胞因子位点周围局部染色质环境的变化，以确定这些早期变化是否为随后的效应分化奠定了基础，因此可能是细胞命运的重要决定因素。 该提案的科学目的是研究未定型T细胞中T辅助细胞因子早期转录的调节。我们推测，这种早期转录是决定效应细胞最终分化状态的关键步骤。我们将评估细胞因子基因座内染色质重塑对这种早期转录的作用，并将这些事件与分化的效应细胞中的事件进行比较。不适当的T细胞分化与许多病理状态有关，并且是免疫应答的关键决定因素。