In mammals, fusion of two highly differentiated gametes gives rise to a totipotent zygote capable of developing into a whole organism. It coincides with translation and degradation of maternally provided transcripts, initiation of global transcription called zygotic genome activation (ZGA), and “epigenetic reprogramming” of germline chromatin states into an embryonic state. The molecular mechanisms underlying this exquisite reprogramming of cell fate are little understood.
The research project has the goal to identify and characterize transcription factors and chromatin regulators which regulate ZGA in early mouse embryos. We utilize novel and highly sensitive genomic approaches to measure nascent transcription and determine open and modified chromatin landscapes in oocytes and early embryos, wild-type and conditionally deficient for major epigenetic modifiers. We apply computational approaches to identify candidate transcription factors (TFs) and histone modifiers controlling ZGA. We use molecular and developmental biology approaches, combined with live-imaging, to interrogate the function of TFs for ZGA. We further investigate the role of chromatin remodeling during spermatogenesis for gene regulation during embryogenesis. On the one hand, we interrogate the relevance of nucleosome eviction during spermatogenesis, as a possibly epigenetic reprogramming process, for defining embryonic competence. On the other hand, we study the genomic distribution and occupancy levels of nucleosomes in developing and mature male germ cells to estimate probabilities for paternal epigenetic inheritance via nucleosomes.
The project provides a crucial contribution to dissecting molecular mechanisms underlying acquisition of totipotency in mouse embryos. It will deliver basic insights into mechanisms and significance of intergenerational epigenetic inheritance versus reprogramming of germ line chromatin states in early embryos. The obtained findings will inspire basic research on the use of Assisted Reproductive Technologies in human reproductive medicine for treating human male sterility.
