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CAREER: HP1 protein functions in gene regulation and chromatin structure

职业：HP1 蛋白在基因调控和染色质结构中发挥作用

基本信息

批准号：
1552586
负责人：
Nicole Riddle
金额：
$ 115万
依托单位：
University of Alabama at Birmingham
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1552586&HistoricalAwards=false
关键词：
CAREER HP1 protein functions gene

项目摘要

The goal of this project is to understand the molecular mechanisms that determine if the genetic information contained within DNA is accessible to the cellular machinery. DNA in a cell's nucleus is packaged into a complex structure called chromatin, which contains a variety of proteins. These chromatin proteins determine if the information stored in a particular portion of the DNA is accessible (genes are "turned on") or inaccessible (genes are "turned off") as part of a process called gene regulation. The members of the Heterochromatin Protein 1 (HP1) protein family function in chromatin structure in organisms as diverse as yeast and humans. Specifically, this project will examine the role of HP1 proteins in gene regulation and the molecular mechanisms mediating this role. It is essential for an organism's survival and health to "turn on" the correct genes at the correct time and place. The results from this study will improve scientific understanding of why this process sometimes goes wrong and how it might be corrected. In addition to furthering knowledge about chromatin, this study will serve to train minority students in chromatin biology through a summer internship program and support the development of a classroom undergraduate research experience (CURE) specifically targeted to minorities and non-traditional students transferring from community colleges to four-year institutions. This project will use transcriptome analysis of Drosophila lines lacking HP1 proteins and chromatin state information from chromatin immunoprecipitation (ChIP) experiments to evaluate the impact of HP1 proteins on gene expression. This analysis will reveal the contexts in which HP1 proteins function as transcriptional activators or repressors, and how cooperative effects differ from individual effect. Analysis of the impact of HP1 recruitment on nucleosome positioning, chromatin composition, and RNA polymerase dynamics will determine how HP1 proteins impact gene regulation. These experiments will identify the molecular mechanism(s) mediating the effects of HP1 proteins on gene expression. Finally, biochemical analysis of the transcription-start-site-(TSS)-associated HP1 complexes will determine why single HP1 complexes are formed at some TSSs, while others recruit multi-HP1 complexes. The findings will provide the foundation for understanding how this important class of proteins is recruited to their target sites and carries out diverse functions in chromatin structure and gene regulation. By utilizing a multi-faceted approach, this study will link the well-established role of HP1 proteins in heterochromatin formation with their role in gene regulation.This project is co-funded by the Genetic Mechanisms Program in the Division of Molecular and Cellular Biosciences in the Biological Sciences Directorate and by the NSF EPSCoR Program.

该项目的目标是了解决定DNA中包含的遗传信息是否可被细胞机器访问的分子机制。细胞核中的DNA被包装成一种称为染色质的复杂结构，其中含有多种蛋白质。这些染色质蛋白决定了存储在DNA特定部分的信息是可访问的（基因被“打开”）还是不可访问的（基因被“关闭”），这是称为基因调控的过程的一部分。异染色质蛋白1（HP1）蛋白家族的成员在酵母和人类等多种生物体的染色质结构中发挥作用。具体而言，该项目将研究HP1蛋白在基因调控中的作用以及介导这种作用的分子机制。在正确的时间和地点“开启”正确的基因对生物体的生存和健康至关重要。这项研究的结果将提高对为什么这个过程有时会出错以及如何纠正的科学理解。除了进一步了解染色质，这项研究将有助于通过暑期实习计划培养少数民族学生染色质生物学，并支持专门针对少数民族和非传统学生的课堂本科研究经验（CURE）的发展从社区学院转到四年制院校。该项目将使用转录组分析缺乏HP1蛋白的果蝇品系和来自染色质免疫沉淀（ChIP）实验的染色质状态信息来评估HP1蛋白对基因表达的影响。这一分析将揭示HP1蛋白作为转录激活因子或抑制因子发挥作用的背景，以及协同效应与个体效应的差异。分析HP1募集对核小体定位、染色质组成和RNA聚合酶动力学的影响将确定HP1蛋白如何影响基因调控。这些实验将鉴定介导HP 1蛋白对基因表达的影响的分子机制。最后，转录起始位点（TSS）相关的HP1复合物的生化分析将确定为什么在某些TSS形成单HP1复合物，而其他招募多HP1复合物。这些发现将为理解这类重要的蛋白质如何被招募到其靶位点并在染色质结构和基因调控中发挥多种功能提供基础。通过利用多方面的方法，这项研究将连接HP1蛋白在异染色质形成中的既定作用与它们在基因regulation.This项目中的作用是共同资助的遗传机制计划在生物科学理事会的分子和细胞生物科学部门和NSF EPSCoR计划。