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

• Published in: Nature communications 2023-03, Vol.14 (1), p.1753-20, Article 1753
• Main Authors: Alexander, Adriana K., Rice, Edward J., Lujic, Jelena, Simon, Leah E., Tanis, Stephanie, Barshad, Gilad, Zhu, Lina, Lama, Jyoti, Cohen, Paula E., Danko, Charles G.
• Format: Article
• Language: English
• Subjects: 13/1; 14; 14/19; 14/63; 38/15; 38/23; 38/39; 38/91; 631/136/2434/1822; 631/208/191/2018; 631/208/200; Accessibility; Animals; Biological activity; Chromatin; Chromatin - genetics; Chromosomes; DNA-directed RNA polymerase; Gametocytes; Gene Expression Regulation; Gene regulation; Genomes; Homologous recombination; Homology; Humanities and Social Sciences; Male; Mammals; Mammals - genetics; Meiosis; Meiosis - genetics; multidisciplinary; Myc protein; Nuclear Proteins - metabolism; Pachytene; Prophase; Proto-Oncogene Proteins - metabolism; Ribonucleic acid; RNA; RNA polymerase; RNA polymerase II; RNA Polymerase II - genetics; Science; Science (multidisciplinary); Spermatocytes; Trans-Activators - metabolism; Transcription activation; Transcription factors; Yeast
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-37408-w

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. During spermatogenic meiosis, chromatin changes due to transcription, homologous recombination, and chromosome synapsis must be coordinated. Here they show that A-MYC and BRDT regulate release of paused RNA PolII to induce a transcriptional burst during pachytene of prophase I.