Regulation of meiotic gene expression
Dynamic gene expression patterns direct the specialized, coordinated and tightly regulated events that culminate in the production of gametes. The regulatory principles and mechanisms underlying the modulation of gene expression during gametogenesis, particularly on a post-transcriptional level, are poorly understood in mammals.
We and others recently identified an RNA binding protein, YTHDC2, as an essential player in the germlines of male and female mice, specifically in transitioning from spermatogonial (mitotic) to spermatocyte (meiotic) gene expression programs. YTHDC2 is an evolutionarily ancient factor, present in the last common ancestor of Metazoa and constitutes a novel pathway that plays a likely conserved function in regulating germ cell fate and differentiation. YTHDC2 has 3′→5′ RNA helicase activity in vitro, and similarity within its YTH domain to an N6-methyladenosine (m6A) recognition pocket that may recognize m6A-modified RNAs. However, its mode of action is unknown.
We are utilizing a combination of experimental approaches to probe the molecular mechanism and physiological functions of YTHDC2, as well as learn about both regulation of meiotic progression and post-transcriptional regulation of RNA during gametogenesis.