Structural Studies of Spt6

Spt6的结构研究

• 批准号: 6937306
• 负责人: SEAN J JOHNSON
• 金额: $ 4.4万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6937306
• 关键词: DNA directed RNA polymerase; chromatin; crystallization; enzyme activity; gel mobility shift assay; gene expression; gene rearrangement; macromolecule; molecular genetics; nucleosomes; postdoctoral investigator; protein protein interaction; protein structure function; transcription factor

DESCRIPTION (provided by applicant): Regulation of gene expression is fundamental to cell function and viability. Disruption of gene expression is a universal feature of tumorigenesis. The enzyme responsible for expression of protein-encoding genes at the level of transcription, RNA polymerase II (RNAPII), is intricately controlled by a variety of essential factors. In addition, the chromatin status of a gene plays a critical role in its expression. Spt6 is a highly conserved and essential eukaryotic protein that functions both as a transcription elongation factor and as a regulator of chromatin structure. The aim of this research is to examine the molecular basis for Spt6 function in transcription and chromatin reorganization by determining crystal structures of Spt6 and relevant complexes. Direct interactions with Spt6 will be identified and characterized by biochemical analysis. Potential interactions with nucleosome structures will be pursued. Tex, a well conserved but poorly understood prokaryotic homolog of Spt6, will also be targeted for structural analysis. A particular focus is to characterize common features between Tex and Spt6, including interactions with the RNA processing exosome/degradosome complexes.

描述（由申请人提供）： 基因表达的调节是细胞功能和生存力的基础。基因表达的破坏是肿瘤发生的普遍特征。负责在转录水平（RNA聚合酶II（RNAPII））表达蛋白质编码基因的酶由多种基本因素精致控制。另外，基因的染色质状态在其表达中起关键作用。 SPT6是一种高度保守且必需的真核蛋白，既可以作为转录伸长因子，又是染色质结构的调节剂。这项研究的目的是通过确定SPT6和相关复合物的晶体结构来检查转录和染色质重组中SPT6功能的分子基础。与SPT6的直接相互作用将通过生化分析确定和特征。将追求与核小体结构的潜在相互作用。 Tex是SPT6的一种保守但知之甚少的原核力同源物，也将用于结构分析。一个特别的重点是表征Tex和Spt6之间的共同特征，包括与RNA加工外泌体/降解体配合物的相互作用。