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Epigenetic Reprogramming, Inheritance and Memory: Dissect epigenetic transitions at fertilisation and early embryogenesis

Project description

Do we pass only DNA to our offspring?

Oocytes and sperm are the germline cells that through fertilisation produce a zygote with the capacity to give rise to all tissues in the body. Early conceptions about the epigenetic reprogramming of germline cells to achieve totipotency have been challenged by recent evidence demonstrating the transfer of parental epigenetic information. The EU-funded EpiRIME project aims to elucidate the mechanisms of epigenetic reprogramming in the zygote as well as how parental epigenetic information is inherited. EpiRIME results will provide fundamental insight into mechanisms with profound consequences for embryonic gene expression and development.

Objective

During gametogenesis, germ cells undergo profound chromatin reorganisation, condensation and transcriptional shutdown. Upon fertilization, gamete chromatin is epigenetically reprogrammed, generating a totipotent zygote that can give rise to all cell types of the adult organism. The maternal factors that reprogram gametes to totipotency are unknown. The current dogma suggests that the parental epigenetic information must be erased in order to establish totipotency.
In contrast, we have recently discovered that maternal gametes transmit the epigenetic H3K27me3 histone modification to the next generation (Zenk et al., Science, 2017) adding to increasing evidence suggesting that gametes convey more than just DNA to the offspring. Nevertheless, the underlying mechanisms and the impact of epigenetic inheritance through the gametes are not yet fully resolved. Critically, the mechanisms and impact of (i) paternal gamete reprogramming, (ii) paternal epigenetic inheritance and (iii) de novo establishment of the zygotic epigenome remain essentially unknown.
The objective of this proposal is to unravel the fundamental principles underlying these three major epigenetic transitions in vivo in Drosophila.
We will achieve our objective via three aims: (i) We will investigate the mechanisms underlying the reprogramming of sperm chromatin at fertilization. Specifically, we will determine the nature and extent of the contributions of two proteins essential for sperm chromatin reprogramming (ii) We will examine the mechanism of histone H3K27me3 inheritance through the paternal germline (iii) We will genetically dissect the de novo establishment of constitutive heterochromatin in the newly formed zygote.
Our investigations of these epigenetic transitions are expected to reveal novel insights into the first steps in the formation of life, and to ultimately advance reproductive and regenerative medicine.

Host institution

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Net EU contribution
€ 1 997 500,00
Address
HOFGARTENSTRASSE 8
80539 Munchen
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
Links
Total cost
€ 1 997 500,00

Beneficiaries (1)