A role of histone modification in homologous chromosome alignment during Caenorhabditis elegans meiosis

智力优势减数分裂过程中同源染色体的初始识别和排列机制是有性生殖生物遗传的重要基础。本研究的总体目标是以线虫秀丽隐杆线虫为模型，通过组蛋白修饰来确定同源染色体的初始排列机制。初步数据表明，MRG-1（一种假定的组蛋白修饰酶的成分）的功能缺失突变体在初始同源比对过程中表现出缺陷。这种缺陷似乎不是减数分裂基因表达改变的间接后果，减数分裂基因表达改变可能是由组蛋白修饰的变化引起的。基于这些和其他的初步研究，假设含有mrg -1的组蛋白修饰酶催化的特定组蛋白修饰状态直接促进了同源染色体的初始排列。这个想法将用生化和遗传的方法来解决。这项研究的成功完成将通过提出组蛋白修饰影响同源染色体之间相互作用的新概念，促进对染色体动力学的基本理解。更广泛的影响本研究将在几个方面有助于提高遗传学和染色体生物学本科生的科学素养。第一，本研究将为本科生提供充足的前沿科研训练机会。其次，一些本科生将进行一个荣誉论文项目，在这个项目中，他们也将学习如何根据他们所进行的研究撰写论文。第三，更大的本科生群体将接触到同龄人在染色体结构和功能的高级研讨会课程中所做的研究。此外，本研究还包括通过直接参与研究，参加讨论小组和期刊俱乐部，以及作为本科生和/或轮转研究生的导师，培养博士后成为独立研究人员。

Intellectual MeritThe mechanism for initial recognition and alignment between homologous chromosomes during meiosis is an essential basis of genetic inheritance in sexually reproducing organisms. The overall objective of this research is to define a mechanism for initial alignment of homologous chromosomes through histone modification using the nematode, Caenorhabditis elegans as a model. Preliminary data indicate that a loss-of-function mutant of MRG-1, a component of a putative histone-modifying enzyme, exhibits a defect in the initial homologous alignment process. This defect does not seem to be an indirect consequence of altered expression of meiotic genes that could potentially result from a change in histone modification. Based on these and other preliminary studies, the hypothesis is that a particular state of histone modification catalyzed by the MRG-1-containing histone-modifying enzyme directly facilitates initial alignment of homologous chromosomes. This idea will be addressed using biochemical and genetic approaches. Successful completion of this research will advance fundamental understanding of chromosome dynamics by presenting the novel concept that histone modification affects interactions between homologous chromosomes. Broader ImpactsThis research will contribute to raising the scientific literacy among undergraduate students in genetics and chromosome biology in several ways. First, this research will provide ample opportunities for cutting-edge scientific research training to undergraduate students. Second, some undergraduate students will conduct an honors thesis project, in which they will also learn how to write a thesis based on the research that they conduct. Third, a larger group of undergraduates will be exposed to the research conducted by their peers in an upper-level seminar course focusing on chromosome structure and function. In addition, this research also involves training a postdoctoral fellow to become an independent researche through direct participation in the research, in discussion groups and journal clubs, and as a mentor to undergraduate students and/or rotation graduate students.