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

Adriana K. Alexander, Edward J. Rice, Jelena Lujic, Leah E. Simon, Stephanie Tanis, Gilad Barshad, Lina Zhu, Jyoti Lama, Paula E. Cohen () and Charles G. Danko ()
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Adriana K. Alexander: Cornell University
Edward J. Rice: Cornell University
Jelena Lujic: Cornell University
Leah E. Simon: Cornell University
Stephanie Tanis: Cornell University
Gilad Barshad: Cornell University
Lina Zhu: Cornell University
Jyoti Lama: Cornell University
Paula E. Cohen: Cornell University
Charles G. Danko: Cornell University

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: Abstract 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 ~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.

Date: 2023
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DOI: 10.1038/s41467-023-37408-w

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