406회 A genetic screen for factors mediating the interaction between PI…

406회

연사 : 박 병 재, 한림대학교 생명과학과

제목 : A genetic screen for factors mediating the interaction between PIE-1, a germline specific inhibitor, and a NURD-like chromatin regulator in C. elegans.

ABSTRACT

Recent studies in Caenorhabditis elegans implicate PcG-and NuRD-like chromatin regulators in the establishment and maintenance of germline-soma distinctions. Somatic cells appear to utilize NuRD-related nucleosome-remodeling factors to overwrite germline-specific chromatin states that are specified through PcG-like activities. The germline, in turn, may rely on an asymmetrically inherited inhibitor to prevent chromatin reorganization that would otherwise erase pluripotency. The NuRDcomplex is required for repressing germline fate in somatic cells during early development. This putative chromatin-remodeling factor contains the zinc-finger protein MEP-1, the Mi-2 homolog LET-418 and the histone deacetylase HDA-1. We previously proposed that PIE-1, a germline-specific protein that binds this complex, inhibits the MEP-1 complex activity and described a genetic screen to investigate mechanisms of MEP-1 complex regulation. In order to identify factors that mediate the repressive interaction between PIE-1 and the MEP-1 complex, we conducted a genetic screen based on the phenotype that results from ectopic expression of pie-1 in somatic cells. Animals expressing pie-1 from the hsp16-41 (heat shock protein) promoter mimic the loss-of-function mep-1 or let-418 mutants, causing the derepression of germline-specific gene (pgl-1) expression in numerous somatic cells and penetrant synMuvB (synthetic multivulva) defect resulting from the deregulation of the vulval differentiation potential. We have analyzed approximately 20,000 mutagenized haploid genomes in conjunction with four secondary screens and isolated 73 mutants that showstrong suppression of the Muv defect caused by PIE-1 expression. These mutants appear to fall into a large number of complementation groups (34 or more) but can be categorized into several distinct classes based on the phenotype.