Resistance of reprogramming after nuclear transfer is mediated by multiple chromatin repressive pathways

Archive ouverte

Beaujean, Nathalie | David, Sarah-Anne | Brochard, Vincent | Jullien, Jérôme | Gurdon, John

Edité par CCSD -

International audience. Reprogramming by Nuclear Transfer (NT) has caught the interest of many research groups due to the opportunity of testing nuclear potency. Moreover, the opportunity to clone by NT has been achieved in a variety of mammalian species and has potential applications for human health, improvement of agriculture species, protection of exotic and endangered species, as well as the advancement of basic biological research. On the other hand, the overall efficiency of producing live cloned offspring is quite low. Although many species can now be cloned, most SCNT embryos undergo developmental arrest before or soon after implantation and the success rate of live offspring production remains very low.Many studies are pointing out the different epigenetic constraints seen in NT embryos, such as aberrant DNA methylation patterns as well as abnormal histone modification patterns. Indeed, even though chromatin remodeling is imposed by the oocyte reprogramming factors on the donor nucleus, the switch from a “somatic” configuration to an embryonic one is often not well achieved. H3K9me3 and H3K27me3 are two repressive modifications suspected to be involved in the resistance to reprogramming after nuclear transfer. In our last study, we provide evidence that H2A ubiquitylation is also contributing to resistance to transcriptional reprogramming in mouse nuclear transfer embryos. We identified mouse genes that are resistant to reprogramming by oocyte factors and demonstrate that deubiquitylation of H2A upon USP21 over-expression can overcome this resistance.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion