News from the CRG
Led by ICREA research professors at the Centre for Genomic Regulation, Luciano Di Croce and Marc A. Marti-Renom, the study focused on a set of genes with what’s known as bivalent promoters – two-way genetic ‘control switches’ that are poised either to turn on in early development and rapidly drive high levels of gene activity, or to switch off and shut down the gene completely. These genes play essential roles in early development where cells have to make quick decisions about which fate to adopt, so the poised switches allow them to quickly flip into the correct pattern of gene activity.
This two-way gene switches mechanism is a fine tuning control system which allows cells to quickly activate or inhibit genes during early embryonic development but it can be also involved in cancer. Previous work had already shown that there are opposing types of chemical ‘tags’, known as histone modifications, that are present on these two-way switches – one set is associated with gene activation and the other with gene silencing. The active tags are put in place by a molecule called MLL2, while the silencing marks are put on by Polycomb proteins. Polycomb proteins also play important roles in human carcinogenesis and cancer development and progression.
To find out more about the interplay between the two type of histone modifications on the switches, postdoctoral researcher Gloria Mas, first author of the work at Di Croce’s team, studied mouse embryonic stem cells growing in the lab. These cells are capable of changing into all the different tissues in the body, and genes with bivalent switches play a key role in setting them off on the right developmental pathway. “We found that changing the balance of histone modifications at these promoters had profound effects on the activity of these vital genes,” explains Di Croce.
Mas et al. 'Promoter bivalency favors an open chromatin architecture in embryonic stem cells' Nature Genetics (2018).