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)： 基因表达调控是细胞功能和生存的基础。基因表达中断是肿瘤发生的普遍特征。在转录水平上负责蛋白质编码基因表达的酶，RNA聚合酶II(RNAPII)，受到多种必需因子的错综复杂的控制。此外，基因的染色质状态对其表达起着至关重要的作用。Spt6是一种高度保守的真核生物必需蛋白，既是转录延伸因子，又是染色质结构的调节因子。本研究的目的是通过测定Spt6及其相关复合体的晶体结构来研究Spt6在转录和染色质重组中作用的分子基础。与Spt6的直接相互作用将通过生化分析来确定和表征。将寻求与核小体结构的潜在相互作用。TeX是Spt6的一个保守但鲜为人知的原核同源物，也将成为结构分析的目标。特别关注的是描述TeX和Spt6之间的共同特征，包括与RNA处理外体/降解体复合体的相互作用。