Maezawa, S. | Search bioRxiv

bioRxiv2020

Super-enhancer switching drives a burst in germline gene expression at the mitosis-to-meiosis transition

The testis has the most diverse and complex transcriptome of all organs due to bursts in expression of thousands of germline-specific genes. Much of this unique gene expression takes place when mitotic germ cells differentiate and enter into meiotic prophase. Here, we demonstrate that the genome-wide reorganization of super-enhancers (SEs) drives bursts of germline genes after the mitosis-to-meiosis transition. At the mitosis-to-meiosis transition, mitotic SEs dissolve while meiotic SEs are established. Meiotic SEs are associated with the activation of key germline genes, defining the cellular identity of germ cells. This SE switching is regulated by the establishment of meiotic SEs via A-MYB (MYBL1), a key transcription factor for germline genes, and by the resolution of mitotic SEs via SCML2, a germline-specific Polycomb protein required for spermatogenesis-specific gene expression. Prior to the entry into meiosis, meiotic SEs are preprogrammed in mitotic spermatogonia, serving to direct the unidirectional differentiation of spermatogenesis. We identify key regulatory factors for both mitotic and meiotic enhancers, revealing a molecular logic for the concurrent activation of mitotic enhancers and suppression of meiotic enhancers in the somatic and/or mitotically proliferating phase.

developmental biology↗

bioRxiv2020

Endogenous retroviruses drive species-specific germline transcriptomes in mammals

Gene regulation in the germline ensures the production of high-quality gametes, long-term maintenance of the species, and speciation. Germline transcriptomes undergo dynamic changes after the mitosis-to-meiosis transition in males and have been subject to evolutionary divergence among mammals. However, the mechanism that underlies germline regulatory divergence remains undetermined. Here, we show that endogenous retroviruses influence species-specific germline transcriptomes in mammals. We show that the expression of endogenous retroviruses, particularly the evolutionarily young K family (ERVK), is associated with gene activation after the mitosis-to-meiosis transition in male mice. We demonstrate that accessible chromatin and H3K27ac, a marker of active enhancers, are tightly associated with ERVK loci as well as with the activation of neighboring evolutionarily young germline genes. Thus, ERVKs serve as evolutionarily novel enhancers in mouse spermatogenesis. These ERVK loci bear binding motifs for critical regulators of spermatogenesis such as A-MYB. The genome-wide transposition of ERVKs might have rewired germline gene expression in a species-specific manner. Notably, these features are present in human spermatogenesis, but independently evolved ERVs are associated with expression of germline genes, demonstrating the prevalence of ERV-driven mechanisms in mammals. Together, we propose a model whereby species-specific transcriptomes are fine-tuned by endogenous retroviruses in the mammalian germline.

developmental biology↗