Elsevier

Molecular Metabolism

Volume 5, Issue 10, October 2016, Pages 1033-1041
Molecular Metabolism

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

https://doi.org/10.1016/j.molmet.2016.08.006Get rights and content
Under a Creative Commons license
open access

Highlights

  • 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.

Abstract

Objective

DNA methylation may be a stable epigenetic contributor to defining fat cell lineage.

Methods

We 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.

Results

Our 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.

Conclusions

Our data suggest that DNA methylation may play an important role in lineage-specific development in adipocytes.

Keywords

Brown adipogenesis
White adipogenesis
DNA methylation
Hoxc10
Next generation sequencing

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