Inter-individual variation of dietary fat-induced mesoderm specific transcript in adipose tissue within inbred mice is not caused by altered promoter methylation

Abstract

Mesoderm specific transcript (Mest), an imprinted gene associated with fat mass expansion under conditions of positive energy balance, shows highly variable expression (~80-fold) in white adipose tissue (WAT) of C57BL/6J (B6) mice fed an obesogenic diet.  Since B6 mice are essentially genetically invariant and Mest is known to be regulated by CpG methylation within its immediate proximal promoter, the large variability in its expression in adipose tissue has the hallmarks of being controlled via an epigenetic mechanism. In this study, bisulfite sequencing and allelic discrimination analyses were performed to determine whether variations in CpG methylation within the Mest promoter were associated with its expression.  Results showed no relationship between CpG methylation in the Mest promoter and high versus low expression in either WAT or isolated adipocytes; and, experiments using a single nucleotide polymorphism in the Mest promoter region between B6 and Castaneus mice showed the expected pattern for an imprinted gene with all maternal alleles being methylated.  These data suggest that mechanisms independent of the CpG methylation status of the Mest promoter must underlie the control of its expression during adipose tissue expansion.