A-MYB and BRDT-dependent RNA Polymerase II pause release orchestrates transcriptional regulation in mammalian meiosis

During meiotic prophase I, spermatocytes must balance transcriptional activation with homologous recombination and chromosome synapsis, biological processes requiring extensive changes to chromatin state. We explored the interplay between chromatin accessibility and transcription through prophase I of mammalian meiosis by measuring genome-wide patterns of chromatin accessibility, nascent transcription, and processed mRNA. We find that Pol II is loaded on chromatin and maintained in a paused state early during prophase I. In later stages, paused Pol II is released in a coordinated transcriptional burst mediated by the transcription factors A-MYB and BRDT, resulting in similar to 3-fold increase in transcription. Transcriptional activity is 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 reveal mechanisms underlying chromatin specialization in either transcription or recombination in meiotic cells.

Automated summary

During meiotic prophase I, balance between transcriptional activation and homologous recombination is crucial. We investigated the interplay between chromatin accessibility and transcription through prophase I and found that Pol II is initially in a paused state and later released in a burst mediated by transcription factors A-MYB and BRDT. This transcriptional activity is separate from meiotic recombination, which shows earlier chromatin accessibility and distinct loci from transcriptional activation. Our findings reveal mechanisms underlying chromatin specialization in transcription or recombination during meiosis.