Dynamic DNA methylation landscape defines brown and white cell specificity during adipogenesis.
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.
School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
Yen Ching
YC
Lim
Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
Sook Yoong
SY
Chia
School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Shengnan
S
Jin
Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), Singapore 138667, Singapore.
Weiping
W
Han
School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: cmding@gmail.com.
Chunming
C
Ding
Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore; Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore. Electronic address: sun.lei@duke-nus.edu.sg.
Lei
L
Sun
Brown adipogenesis; DNA methylation; Hoxc10; Next generation sequencing; White adipogenesis
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