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.

该项目探讨了真核细胞染色体在不改变DNA序列的情况下，在基因控制中产生和保持可遗传变异的细胞过程的本质。这些过程在实验上很容易研究，当它们对影响彩色色素产生的基因进行操作或在其附近进行操作时。参数突变是一个用来描述这样一个过程的术语，在这个过程中，亲本染色体之间的相互作用导致基因调控中的可遗传变化。植物和动物中的辅助性交的例子似乎违反了孟德尔的遗传学第一定律，即基因在有性传播后保持不变。因此，参数化过程挑战了现代生物学的基本假设，并提出了关于“遗传”变异的起源和维持的新概念。该项目将利用生物化学、分子生物学、突变和系谱分析来确定特定的基因组序列和相关的分子变化，这些变化与玉米紫色植株1(PL1)基因座上发生的这些动态行为有关。在功能上定义PL1基因这些区域的突变，以及识别至少九个其他完整的辅助性机制组成部分的突变，将被用于实现这些目标。这项研究将澄清调节这些动态行为的基因组序列的类型，并揭示负责传递可遗传的、非DNA编码的调节信息的染色体修改类型。识别易受突变影响的基因组区域将有助于破译测序的真核生物基因组的重要调控信息。该项目的其他更广泛的影响包括在植物生物学、遗传学和染色体结构/功能关系领域为研究生、代表不足的少数族裔本科生和高中生提供教育和研究培训。了解真核遗传学的这一特殊机制有望对当前与农业基本问题有关的研究产生影响。