Description du projet
Ne transmettons-nous que l’ADN à notre descendance?
Les ovocytes et le sperme sont les cellules germinales qui, grâce à la fertilisation, produisent un zygote capable de générer tous les tissus du corps. Les premières conceptions de la reprogrammation épigénétique des cellules germinales pour parvenir à la totipotence ont été remises en question par de récentes données démontrant le transfert d’informations épigénétiques des parents. Le projet EpiRIME, financé par l’UE, entend comprendre les mécanismes de la reprogrammation épigénétique dans le zygote ainsi que la manière dont les informations épigénétiques des parents sont héritées. Les résultats d’EpiRIME fourniront des connaissances fondamentales sur les mécanismes ayant de lourdes conséquences sur l’expression génétique et le développement de l’embryon.
Objectif
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.
Champ scientifique
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
80539 Munchen
Allemagne