Molecular Mechanisms Controlling Heritable Epigenetic Variation

控制遗传性表观遗传变异的分子机制

• 批准号: 0419909
• 负责人: Jay Hollick
• 金额: $ 54.3万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0419909&HistoricalAwards=false
• 关键词: Molecular; Mechanisms; Controlling; Heritable; Epigenetic

This project addresses the nature of cellular processes by which eukaryotic chromosomes generate and maintain heritable variation in gene control without altering DNA sequence. These processes are experimentally simple to study when they operate on, or nearby, genes affecting the production of colorful pigments. Paramutation is a term used to describe one such process in which interactions between parental chromosomes lead to heritable alterations in gene regulation. Examples of paramutation in both plants and animals appear to violate Mendel's first law of genetics that genes remain unchanged following sexual transmission. The paramutation process thus challenges fundamental assumptions of modern biology and presents novel concepts regarding the genesis and maintenance of 'genetic' variation. This project will employ biochemistry, molecular biology, mutational and pedigree analyses to identify specific genomic sequences and associated molecular changes responsible for these dynamic behaviors occurring at the purple plant 1 (pl1) locus in corn. Mutations that functionally define these regions at the pl1 gene as well as mutations that identify at least nine other integral components of the paramutation mechanism will be used to achieve these aims. This research will clarify the types of genome sequences that moderate these dynamic behaviors and reveal the types of chromosome modifications responsible for transmitting heritable, non-DNA encoded, regulatory information. Identification of genomic regions susceptible to paramutation will aid in deciphering important regulatory information of sequenced eukaryotic genomes. Further broader impacts of the project include providing educational and research training outreach in the areas of plant biology, genetics, and chromosome structure/function relationships for both graduate students, underrepresented minority undergraduates and high school students. Understanding this particular mechanism of eukaryotic genetics promises impacts to current research related to fundamental issues of agriculture.

该项目探讨了真核染色体在不改变 DNA 序列的情况下产生和维持基因控制中可遗传变异的细胞过程的本质。当这些过程作用于影响彩色颜料生产的基因或附近时，这些过程在实验上很容易研究。副突变是一个术语，用于描述这样一个过程，其中亲本染色体之间的相互作用导致基因调控的可遗传改变。植物和动物中的副突变例子似乎违反了孟德尔遗传学第一定律，即基因在性传播后保持不变。因此，副突变过程挑战了现代生物学的基本假设，并提出了有关“遗传”变异的发生和维持的新概念。该项目将采用生物化学、分子生物学、突变和谱系分析来识别特定的基因组序列和相关的分子变化，这些变化负责玉米紫色植物 1 (pl1) 基因座发生的这些动态行为。在功能上定义 pl1 基因的这些区域的突变以及识别副突变机制的至少九个其他组成部分的突变将用于实现这些目标。这项研究将阐明调节这些动态行为的基因组序列类型，并揭示负责传递可遗传的、非 DNA 编码的调控信息的染色体修饰类型。鉴定易受副突变影响的基因组区域将有助于破译已测序的真核基因组的重要调控信息。该项目更广泛的影响包括为研究生、代表性不足的少数族裔本科生和高中生提供植物生物学、遗传学和染色体结构/功能关系领域的教育和研究培训。了解真核遗传学的这种特殊机制有望对当前与农业基本问题相关的研究产生影响。