Scientists at Karolinska Institutet and Gurdon Institute in Cambridge, United Kingdom have identified a novel mechanism allowing pluripotent stem cells to maintain their genome in an unpacked state.
Embryonic stem cells and induced pluripotent stem cells have the ability to give rise to all cell types present in the adult body. In order to maintain this immature state, genes that are turned on in specialized cells must remain inactive in pluripotent cells, but ready to be quickly activated upon maturation into a cell in the skin or liver. The genome of a cell is packed in the nucleus, more specifically in a structure called chromatin. If the chromatin packing is tight (condensed), activatory molecules are not able to access parts of the genome that control the activation of genes. Therefore, for a certain gene to be activated, the chromatin structure must be unpacked (decondensation). Pluripotent stem cells are unique in that their genome is partially unpacked (chromatin decondensation), when compared to specialized cells, to allow rapid activation of differentiation genes upon a given stimuli.
In a new study, published in Nature, the scientists have been able to identify a specific enzymatic activity, called citrullination, that contributes to decondensed chromatin state in pluripotent cells. Gonçalo Castelo-Branco, principal investigator at Karolinska Institutet and co-first author in the study with Maria Christophorou of the Gurdon Institute, explained that “the genome (DNA) is highly negatively charged and is associated in the chromatin structure with proteins called histones, which are highly positively charged. We found that in pluripotent cells, citrullination reduces the charge of some histones, weakening their association with the genome and contributing to decondensation.”