Epigenetic Regulation of the X chromosome in C. elegans

Yale University, New Haven CT

Investigators

Abstract

Noncoding RNA's play critical, though poorly understood, roles in epigenetic mechanisms of gene regulation. The epigenetic control of gene regulation by dosage compensation is required to equalize sex chromosome expression between two sexes with differing numbers of sex chromosomes. Strikingly, both mammals and Drosophila require the action of noncoding RNA's in order to distinguish the X chromosomes from autosomes and correctly implement dosage compensation, although the mechanisms of dosage compensation evolved independently in these organisms. In C. elegans, the mechanism by which the dosage compensation complex recognizes the X chromosome remains unknown. The focus of this research is a C. elegans X-linked noncoding RNA identified in the laboratory through bioinformatics. This noncoding RNA is restricted to the nuclei of virtually all somatic cells. It localizes specifically to a number of small subnuclear regions corresponding to the number of X chromosomes present. This research tests the hypothesis that this noncoding RNA functions as a component of an X chromosome recognition mechanism in C. elegans. The localization of the noncoding RNA to the X chromosome will be assessed, and the effects of a deletion mutant of this gene on hermaphrodite and male viability will be determined. Specifically, this study will lead to insight regarding the mechanism of X chromosome recognition in C. elegans. More broadly, this work will generate a more thorough understanding of the chromosome-wide regulation of transcription by epigenetic modifications involving noncoding RNA's. The manner in which groups of genes on chromosomes are coordinately activated or repressed is a basic problem in biology. Recently, researchers have discovered that diverse long-term and long-range effects on coordinated gene regulation require the action of certain gene products that function as RNA, not protein. The roles and requirements for these RNA's in long-range gene regulation are poorly understood. In this research program, the genetic, microscopic, and transgenic tools available for C. elegans research will facilitate investigation into the requirement for a candidate noncoding RNA.