Fig. 3

Schematic representation of the changes in 3D contacts and expression associated with MLH1 promoter methylation. In control cells (derived from CME’s relatives), MLH1 promoter is unmethylated and both alleles show the same pattern of interactions regardless of the c.-93 genotype, with concomitant biallelic expression of MLH1. In cells carrying the epimutation (epimutant cells) the MAA allele is methylated independently of the c.-93 genotype. MLH1 methylation and loss of transcription are coupled to changes in the 3D promoter interactions. Regulatory elements in physical contact with the MLH1 promoter can harbour genetic variants in cis with the MAA that may alter binding of TFs and could predispose to MLH1 epimutation