Wellcome Trust Sir Henry Dale fellowship pre-application: Chih-Jen Lin
Title: Acquisition of competence in the oocytes: epigenetic regulation of ribosomal RNA transcription.
Background: The Oocyte, a highly differentiated cell type, has the remarkable capacity to reprogram cells (from sperm to even somatic cells) to that of totipotent embryonic cells. Understanding how oocyte-derived factors contribute to developmental competence will not only impact the fields of stem cell biology/cellular reprogramming but also benefit to infertile patients directly. I have recently shown that Hira mediated histone variant H3.3 incorporation is involving the nucleosome assembly in the male genome to form a male pronucleus. Moreover, I demonstrated that maternal H3.3 is required for zygotic cleavage to 2-cells by regulating the function of RNA Polymerase I (ribosomal RNA, rRNA, transcription). This serendipity overturned a long-lasting dogma that transcription of the mouse zygotic genome is minor and not required for development. However, the molecular mechanisms remain to be elucidated. RRNAs are transcribed using rDNA gene array, which is an epigenetically regulated repeated gene locus. My overall hypothesis is that unique epigenetic regulatory mechanisms of ribosome RNA transcription occur during oogenesis is critical for zygote development. To prove this, I will continue explore how Hira complex and H3.3 regulate rDNA transcription. I will next explore the upstream processes of ribosome