Genome architecture and totipotency: An intertwined relation during early embryonic development

Chromosomes are not randomly packed and positioned into the nucleus but folded in higher‐order chromatin structures with defined functions. However, the genome of a fertilized embryo undergoes a dramatic epigenetic reprogramming characterized by extensive chromatin relaxation and the lack of a defined three‐dimensional structure. This reprogramming is followed by a slow genome refolding that gradually strengthens the chromatin architecture during preimplantation development. Interestingly, genome refolding during early development coincides with a progressive loss of developmental potential suggesting a link between chromatin organization and cell plasticity. In agreement, loss of chromatin architecture upon depletion of the insulator transcription factor CTCF in embryonic stem cells led to the upregulation of the transcriptional program found in totipotent cells of the embryo, those with the highest developmental potential. This essay will discuss the impact of genome folding in controlling the expression of transcriptional programs involved in early development and their plastic‐associated features. Depletion of CTCF in pluripotent ESC activates the transcriptional program found in totipotent embryos. Importantly, embryonic chromatin undergoes a progressive genome refolding during early development concomitant with increased CTCF expression and loss of developmental potential. In this essay, we discuss the intertwined relation between chromatin architecture and cell potential.