Periodic Reporting for period 3 - Totipotency (Transcriptional and Epigenetic Regulation of Totipotency in Mouse Early Embryos.)
Reporting period: 2019-08-01 to 2021-01-31
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 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. By transferring nuclei of immature and mature male germ cells into oocytes, we interrogate the relevance of nucleosome eviction during spermatogenesis, as a possibly epigenetic reprogramming process, for defining embryonic competence.
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.