GSE212117
Meiotic gene transcription programs are mediated by A-MYB and BRDT-dependent RNA Pol II pause release during mammalian prophase I [ATAC-Seq]
During meiotic prophase I, germ cells must balance transcriptional activation with meiotic recombination and chromosome synapsis, biological processes requiring extensive changes to chromatin state and structure. Here we explored the interplay between chromatin accessibility and transcription across a detailed time-course of murine male meiosis by measuring genome-wide patterns of chromatin accessibility, transcription, and processed mRNA. To understand the relationship between these parameters of gene regulation and recombination, we integrated these data with maps of double-strand break formation. Maps of nascent transcription showed that Pol II is loaded on chromatin and maintained in a paused state early during meiosis. In pachynema, paused Pol II is released in a coordinated transcriptional burst resulting in ~3-fold increase in transcription. Release from pause is mediated by the transcription factor A-MYB and the testis-specific bromodomain protein, BRDT. The burst of transcriptional activity is both temporally and spatially segregated from key steps of meiotic recombination: double strand breaks show evidence of chromatin accessibility earlier during prophase I and at distinct loci from those undergoing transcriptional activation, despite shared chromatin marks. Our findings uncover the mechanisms of transcriptional activation and how cells compartmentalize transcription and recombination during meiosis. Overall design: Assay for Transposase Accessible Chromatin and Sequencing (ATAC-seq) samples for prophase I substages: Leptonema/Zygonema, Pachynema, and Diplonema.  Raw fastq files and bigWig files are provided.