LAUSR

BACKGROUND The germline perpetuates genetic information across generations. To maintain the integrity of the germline, transposable elements (TEs) 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 TEs, including DNA methylation, RNA interference, and the PIWI-interacting RNA (piRNA) 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 (TFs). 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 6 transcriptional regulators-GLIS3, MYB-A, RB1, RHOX10, SETDB1, and ZBTB16 (PLZF)-are both developmental regulators and TE defense factors. These factors act at different stages of germ cell development, including in pro-spermatogonia (ProSG), spermatogonial stem cells (SSCs), and spermatocytes. Collectively, the data suggests 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. This article is protected by copyright. All rights reserved.