Role of 3D chromatin architecture in zygotic genome activation in the totipotent mouse embryos

• Applicant: Dr. Anastasiia Bondarieva, Ph.D.
• Subject Area: Developmental Biology ; Cell Biology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 519613997

A totipotent zygote is a single cell able to give rise to all germ layers and extraembryonic tissues required for the development of an organism. Remarkably, a zygote is formed by two terminally differentiated gametes, oocyte and sperm, in the process of fertilisation. To acquire a totipotent state, the transcriptionally silent parental genomes undergo epigenetic reprogramming and chromatin reorganisation and subsequently become transcriptionally active during zygotic genome activation (ZGA). The molecular mechanisms underlying the oocyte-to-embryo transition and ZGA are not universal between different organisms and there are large gaps in understanding these fundamental processes in mammalian development. Recently, studies by several laboratories including the Tachibana lab have provided insights into the 3D chromatin architecture during mammalian preimplantation development. These showed that the genome of early embryos is organised in 3D space at different levels. Zygotic chromatin is folded into cohesin-mediated loops that assemble into CTCF-demarcated topologically associated domains (TADs). In mouse embryos, zygotic genome architecture emerges at the time of ZGA initiation and it was shown that the formation of loops and TADs in the early embryo does not depend on transcription. At the same, it is not known whether the establishment of 3D chromatin architecture in the zygote is important for ZGA initiation. I will use mouse genetics, embryo manipulation methods, cutting-edge imaging techniques and genomic methods such as RNA-seq and single-nucleus Hi-C developed in the Tachibana lab to address the question of whether the timely emergence and dynamics of 3D chromatin organisation are required for efficient initiation of embryonic transcription.

• DFG Programme: WBP Position