The RNA Binding Protein Dead End1 Is Differentially Expressed in Male Germ Cells During Late Gestation and Targets Chromatin Modifiers and Translational Machinery

ABSTRACT: DND1 is essential to maintain germ cell identity. Loss of Dnd1 function results in trans-differentiation of germ cells to somatic fates in zebrafish or the formation of teratomas in mice. To explore the mechanistic role of DND1, we recently developed a transgenic mouse line in which a functional fusion protein between DND1 and GFP is expressed from the endogenous locus (Dnd1GFP). Surprisingly, we found that this reporter distinguishes two male germ cell populations (MGCs) during late gestation cell cycle arrest (G0). Most MGCs express low levels of DND1-GFP, but 5-12% of the population express high levels of DND1-GFP. An RNA-seq time course during late gestation revealed that Dnd1 transcript levels as well as transcript levels for multiple epigenetic regulators are 5-10-fold higher in DND1-GFP-hi cells. Furthermore, using antibodies against DND1-GFP for RNA immunoprecipitation (RIP) time course sequencing during late gestation, we identified multiple epigenetic and translational regulators that are binding targets of DND1 during G0. Among these targets are DNA methyltransferases (Dnmts), the enzyme Setdb1 that imposes the nuclear lamina associated repressive histone mark (H3K9me3), five Tudor domain proteins (Tdrds), four actin dependent regulators (Smarcs), and a group of ribosomal and Golgi proteins. These data suggest that DND1 binds to transcripts of a group of epigenetic enzymes and gates their translation during MGC G0 arrest in late gestation.

ORGANISM(S): Mus musculus

PROVIDER: GSE197610 | GEO | 2022/10/18

REPOSITORIES: GEO