Brief CommunicationDynamic DNA methylation landscape defines brown and white cell specificity during adipogenesis

- DNA methylation is a stable epigenetic signature for brown and white adipocyte lineage.
- We identified 31 genes whose promoters were significantly differentially methylated between white and brown adipogenesis.
- Blocking DNA methylation with 5-Aza-cytidine increase the expression of a group of HoxC genes.

ObjectiveDNA methylation may be a stable epigenetic contributor to defining fat cell lineage.MethodsWe performed reduced representation bisulfite sequencing (RRBS) and RNA-seq to depict a genome-wide integrative view of the DNA methylome and transcriptome during brown and white adipogenesis.ResultsOur analysis demonstrated that DNA methylation is a stable epigenetic signature for brown and white cell lineage before, during, and after differentiation. We identified 31 genes whose promoters were significantly differentially methylated between white and brown adipogenesis at all three time points of differentiation. Among them, five genes belong to the Hox family; their expression levels were anti-correlated with promoter methylation, suggesting a regulatory role of DNA methylation in transcription. Blocking DNA methylation with 5-Aza-cytidine increased the expression of these genes, with the most prominent effect on Hoxc10, a repressor of BAT marker expression.ConclusionsOur data suggest that DNA methylation may play an important role in lineage-specific development in adipocytes.