Cell Fate Maintenance and Reprogramming During the Oocyte-to-Embryo Transition

Germ cells are responsible for the delivery of genetic information from one generation to the next and thus provide a physical chain of inheritance. When fertilized, the female gamete, the oocyte, initiates the transition into becoming an embryo that can develop into a new organism. This transition from being an oocyte regulated by maternally deposited factors to becoming an embryo with its own transcriptional program is called the oocyte-to-embryo transition (OET), which encompasses both the removal of maternal factors and embryonic genome activation (EGA). Several factors and mechanisms have been implicated in the regulation of EGA, including transcription factors, chromatin regulators and RNA-binding proteins. Crucial for maintaining oocyte cell fate and the dichotomy between germline and soma, EGA must be repressed in the germ cells. However, the mechanisms through which this regulation is achieved are not well known. In Caenorhabditis elegans, the conserved TRIM-NHL protein LIN-41 has been identified as a regulator of EGA in the C. elegans developing oocytes. LIN-41 is an RNA-binding protein, capable of recognizing stem-loop structures in the untranslated regions of its target mRNAs. In the absence of LIN-41 the meiotic oocytes re-enter a mitotic cell cycle and undergo precocious EGA followed by further differentiation resulting in a teratoma. LIN-41 functions to prevent re-entry into mitosis by repressing translation of cdc-25.3 mRNA, whose product in turn regulates the activity of the cell cycle kinase CDK-1. However, mRNA target(s) of LIN-41, regulated to prevent transcriptional reprogramming and precocious EGA, remain unknown. To close that gap, we have searched for these targets and identified cfp-1, encoding a conserved chromatin modifier, as a novel target of LIN-41 in the developing oocytes. We show that LIN-41 regulates expression of CFP-1. Additionally, we show that that LIN-41 is capable of regulating gene expression through recognition of the conserved LIN-41 response elements (LREs) found in the 3’ untranslated region of cfp-1 mRNA. Our findings suggest a role for CFP-1 in transcriptional reprogramming during OET, and potentially provide a link between the cytoplasmic RNA binding protein LIN-41 and regulation of EGA.