Genome-wide transcriptional silencing and mRNA stabilization allow the coordinated expression of the meiotic program in mice

Abstract

The transcriptional dynamic of mammalian cells when these transit from the ubiquitous mitotic to a meiotic-specific program is key to understand this switch central to sexual reproduction. By quantifying active RNA polymerase II and nascent transcripts using single cell dataset and ethynyl-uridine pool-down with sorted cells from synchronized testes, we detailed the transcriptional activity of murine male germ cells. When spermatogonia differentiate, transcription slows down, reaching minimal activity at meiotic entry and resumes during pachytene stage. This event, we termed EMLT (for early meiotic low transcription), is distinct from the silencing of sex chromosomes as it is independent of Setdb1, though it is accompanied by the same chromatin mark, H3K9me3. EMLT is delayed in Stra8KO but occurs in mutants altering meiotic chromosome structure or double-strand break formation or repair. By comparing transcript abundance and nascent transcription we unveil a massive event of messenger RNA stabilization that parallels EMLT. Altogether our data indicate that meiosis is initiated with a nearly silent genome, and we propose that the stabilization of transcripts at that time facilitates the meiotic entry by synchronizing the expression of several meiotic subprograms.