ISWI1, Chromatin remodeling, and transcription in vivo

ISWI1、染色质重塑和体内转录

• 批准号: 6544168
• 负责人: MICHAEL J PAZIN
• 金额: $ 29.86万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6544168
• 关键词: DNA footprinting; RNase protection assay; T lymphocyte; apoptosis; cell free system; cell proliferation; chromatin; colony stimulating factor; deoxyribonuclease I; enzyme activity; genetic mapping; genetic regulation; genetically modified animals; immunoprecipitation; interleukin 2; interleukin 8; laboratory mouse; leukocyte activation /transformation; northern blottings; nucleoproteins; polymerase chain reaction; protein binding; protein structure function; transcription factor; transfection /expression vector

DESCRIPTION (provided by applicant): Chromatin remodeling (changing chromatin structure) is mediated by enzymes in eukaryotic cells. While several remodeling enzymes have been identified, little is known about how remodeling enzymes regulate gene expression in higher eukaryotes. It is also not known which enzymes regulate which genes, whether they work together, or why there are so many remodeling enzymes in higher eukaryotes. We investigate the role of chromatin remodeling in T cell activation. The experiments proposed use multiple approaches to continue our analysis of energy-dependent remodeling enzymes in higher eukaryotes. We are systematically asking what genes are regulated by which remodeling enzymes. We are using this information to ask what mechanism is used to regulate these target genes. We are also asking what the physiological roles of chromatin remodeling are in living cells. We focus on the remodeling protein hSNF2L, and compare it to the closely related protein hSNF2H and the more distantly related protein BRG1. We use T cell activation as a model system in our experiments, because the transcriptional program is relatively well understood, and also because several T cell genes are known to change chromatin structure during activation-induced gene regulation This program will provide important new information about the mechanism of energy-dependent remodeling enzymes. We will gain new insight into the link between remodeling and transcriptional regulation of mammalian genes. We will also learn about T cell activation, a central process in the immune system controlling lymphocyte development, differentiation and function.

描述（由申请人提供）：染色质重塑（变化的染色质结构）是由真核细胞中的酶介导的。虽然已经鉴定出几种重塑酶，但对于重塑酶如何调节较高真核生物中的基因表达知之甚少。尚不清楚哪种酶调节了哪种基因，它们是否共同起作用，或者为什么在较高的真核生物中有这么多重塑酶。 我们研究了染色质重塑在T细胞激活中的作用。该实验提出的使用多种方法继续我们分析较高的真核生物中能量依赖性重塑酶。我们正在系统地询问哪些重塑酶受到调控哪些基因。我们正在使用此信息询问使用哪种机制来调节这些靶基因。我们还询问染色质重塑的生理作用在活细胞中。我们专注于重塑蛋白HSNF2L，并将其与密切相关的蛋白质HSNF2H和更遥远相关的蛋白BRG1进行比较。我们在实验中使用T细胞激活作为模型系统，因为转录程序相对众所周知，并且还因为已知几个T细胞基因在激活诱导的基因调节过程中会改变染色质结构。 该程序将提供有关能量依赖性重塑酶机制的重要新信息。我们将对哺乳动物基因的重塑和转录调节之间的联系有了新的见解。我们还将了解T细胞激活，这是控制淋巴细胞发育，分化和功能的免疫系统中的中心过程。