Developmental regulators moonlighting as transposons defense factors

Abstract

Background:The germline perpetuates genetic information across generations. To maintain the integrity of the germline, transposable elements in the genome must be silenced, as these mobile elements would otherwise engender widespread mutations passed on to subsequent generations. There are several well-established mechanisms that are dedicated to providing defense against transposable elements, including DNA methylation, RNA interference, and the PIWI-interacting RNA pathway. Objectives:Recently, several studies have provided evidence that transposon defense is not only provided by factors dedicated to this purpose but also factors with other roles, including in germline development. Many of these are transcription factors. Our objective is to summarize what is known about these "bi-functional" transcriptional regulators.Materials and methods: Literature search. Results and conclusion:We summarize the evidence that six transcriptional regulators-GLIS3, MYBL1, RB1, RHOX10, SETDB1, and ZBTB16-are both developmental regulators and transposable element-defense factors. These factors act at different stages of germ cell development, including in pro-spermatogonia, spermatogonial stem cells, and spermatocytes. Collectively, the data suggest a model in which specific key transcriptional regulators have acquired multiple functions over evolutionary time to influence developmental decisions and safeguard transgenerational genetic information. It remains to be determined whether their developmental roles were primordial and their transposon defense roles were co-opted, or vice versa.

New horizons in testis biology and men's health: a special issue of the XXVIth North American testis workshop

“…Several manuscripts address the complexities and stage-specific regulation of gene expression throughout spermatogenesis from fetal life, discussing the role of TET proteins, by Dr. Marisa Bartolomei, 10 in fetal and early postnatal life from Dr. Miles Wilkinson, 11 through to post-mitotic spermatogenesis by Dr. Prabhakara Reddi. 12 How epigenetic factors act and influence spermatogenesis and male fertility is considered in reviews from Dr. Chen Chen discussing the role of piRNA trimming 13 and Dr. John McCarrey presenting his perspective on the importance of epigenetic priming to spermatogonial stem cell fate.…”

“…Several manuscripts address the complexities and stage‐specific regulation of gene expression throughout spermatogenesis from fetal life, discussing the role of TET proteins, by Dr. Marisa Bartolomei, 10 in fetal and early postnatal life from Dr. Miles Wilkinson, 11 through to post‐mitotic spermatogenesis by Dr. Prabhakara Reddi 12 …”