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

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

Intellectual Merit The 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 Impacts This 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.