Molecular mechanisms underlying endogenous retroviral regulation

Endogenous retroviruses (ERVs) can function as cis-regulatory elements, with certain families being co-regulated during preimplantation development in an exquisitely orchestrated manner. Transcription factors such as OCT4, SOX2, and NANOG bind to and transcriptionally activate ERVs, thereby establishing a close connection between ERVs regulation and the identity of pluripotent cells. Yet, much remains unknown. Which repertoire of proteins—transcription factors, epigenetic regulators, and others—regulates each ERV family? Which molecular mechanisms fine-tune ERV activity during development, and how do they shape the critical events of human preimplantation? Do these same mechanisms underlie the aberrant activation of ERVs in pathological contexts, including neurodegeneration and cancer? To address these questions, our lab employs 2D and 3D stem cell models, combined with quantitative approaches, to map the ERV proteome and uncover its role in embryogenesis. Ultimately, building a comprehensive understanding of ERV regulation will illuminate fundamental principles of stem cell biology and it will open new avenues for therapeutic strategies in disease.