In C. elegans, early embryogenesis is partially orchestrated by a well-characterized series of asymmetric cellular divisions, resulting in somatic lineages sequentially separating from P-germ blastomeres. In the early embryo, a number of protective mechanisms exist that appear to shield germline blastomeres from inductive signals that specify the fates of somatic cells. Specifically, germ cells are kept transcriptionally quiescent by the activity of the maternally loaded CCCH protein PIE-1. However, upon the birth of the germ cell precursors Z2 and Z3, PIE-1 disappears. The mechanisms controlling the temporal regulation of PIE-1 in the nascent germ cells, as well as post-PIE-1 repressive processes, are poorly understood. We have previously demonstrated that there is a chromatin based repressive mechanism that succeeds PIE-1 degradation, effectively marking and maintaining the germ lineage. The primordial germ cells Z2/Z3 lose the histone H3 modification K4 dimethylation, a conserved marker for transcriptionally competent chromatin. We have demonstrated that germline-specific chromatin remodeling is defective in the temperature sensitive embryonic arrest mutant
emb-4. In addition, late-stage
emb-4 embryos fail to differentiate properly and arrest as masses of poorly differentiated cells. This defect is accompanied by ectopic expression of the germline-specific marker PGL-1, suggesting an involvement of
emb-4 in the repression of germ cell fate in the soma. In collaboration with the Greenwald lab, we have shown that
emb-4 is allelic to two previously identified mutants including
sel-6, a suppressor of the
lin-12(d) (Notch) mutant (Iskra Katic and Iva Greenwald, personal communication). The
emb-4/sel-6 gene encodes a novel, highly conserved protein with orthologs in fly, mouse and human. Currently we are investigating the molecular and genetic mechanisms by which EMB-4/SEL-6 dictates germline-specific chromatin remodeling and cell fate specification in the embryo.