How chromatin is spatially reorganised during zygotic reprogramming to totipotency

How chromatin is reorganised and reprogrammed after fertilisation to generate a totipotent embryo remain crucial questions in biology. One of our key interests is the mechanism of active DNA demethylation that acts predominantly on the paternal genome of the single-cell embryo or zygotes. To determine how 3D chromatin organisation changes towards a totipotent state, we pioneered single-nucleus Hi-C (snHi-C) and described the changes that occur during the oocyte-to-zygote transition. In order to fully understand zygote biology, we also need to understand its precursor, the oocyte or egg. Chromosome missegregation in oocytes is the main cause of aneuploid pregnancies and spontaneous miscarriages. We are proposing a new hypothesis to explain the increase in chromosome missegregation that leads to trisomic pregnancies with maternal age.

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