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ERC

Totipotency Report Summary

Project ID: 695288
Funded under: H2020-EU.1.1.

Periodic Reporting for period 1 - Totipotency (Transcriptional and Epigenetic Regulation of Totipotency in Mouse Early Embryos.)

Reporting period: 2016-08-01 to 2018-01-31

Summary of the context and overall objectives of the project

In mammals, fusion of the egg and sperm gives rise to a totipotent zygote capable of developing into a whole organism. The change in fate 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 program aims at identifying and characterizing in a comprehensive manner the transcription factors and chromatin regulators that initiate and regulate ZGA in a parental specific manner in early mouse embryos.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In the first 1.5 years of the granting period, we have been generating in depth expression data sets of mouse pre-implantation embryos. We have been performing extensive computational analyses of published and in-house generated genome-wide data sets for RNA and chromatin modifications in such samples. We identified several candidate regulators of zygotic genome activation that we are currently characterizing using functional assays. In addition, we have been characterizing the impact of loss of expression of several chromatin regulators on embryonic development and gene regulation in early embryos. We are in the process of evaluating the significance of possible paternal inheritance of nucleosomes for gene regulation during ZGA and later development.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

To date, we established sensitive state-of-the-art methodologies and gathered comprehensive data sets which give us important leads to possible regulatory mechanisms controlling ZGA. Our research may impact on the use of Assisted Reproductive Technologies (ART) in human reproductive medicine.
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