Fig. 6. The Mediator CDK Module and cohesin play distinct and opposite roles in the genomic distribution of heterochromatin.

A Heterochromatin domains, marked by H3K9me3, cluster together in three-dimensional space, separating the genome in A- and B compartments. B Model for how cohesin and Mediator-CDK may play opposite roles in heterochromatin domain formation. Upon loss of the cohesin-release factor WAPL and stabilization of cohesin, loops increase in size, leading to a loss of compartmentalization. This perturbs the formation and spreading of heterochromatin domains. Loss of members of the Mediator-CDK-Module results in unconstrained heterochromatin-domain amplification and hyper-compartmentalization, impairing cohesin- and CTCF binding and a loss of associated loops.