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Epigenetics. 2014 Sep;9(9):1195-206. doi: 10.4161/epi.29856. Epub 2014 Jul 10.

Methylome, transcriptome, and PPAR(γ) cistrome analyses reveal two epigenetic transitions in fat cells.

Author information

1
Research Center for Stem Cell Engineering; National Institute of Advanced Industrial Science and Technology (AIST); Tsukuba, Japan.
2
Computational Biology Research Center; National Institute of Advanced Industrial Science and Technology (AIST); Tokyo, Japan; Japan Science and Technology Agency; Kawaguchi, Japan.
3
Gene Expression Laboratory; Salk Institute for Biological Studies; La Jolla, CA USA.
4
Gene Expression Laboratory; Salk Institute for Biological Studies; La Jolla, CA USA; Howard Hughes Medical Institute; Salk Institute for Biological Studies; La Jolla, CA USA.

Abstract

Although DNA modification is adaptive to extrinsic demands, little is known about epigenetic alterations associated with adipose differentiation and reprogramming. We systematically characterized the global trends of our methylome and transcriptome data with reported PPAR(γ) cistrome data. Our analysis revealed that DNA methylation was altered between induced pluripotent stem cells (iPSCs) and adipose derived stem cells (ADSCs). Surprisingly, DNA methylation was not obviously changed in differentiation from ADSCs to mature fat cells (FatCs). This indicates that epigenetic predetermination of the adipogenic fate is almost established prior to substantial expression of the lineage. Furthermore, the majority of the PPAR(γ) cistrome corresponded to the pre-set methylation profile between ADSCs and FatCs. In contrast to the pre-set model, we found that a subset of PPAR(γ)-binding sites for late-expressing genes such as Adiponectin and Adiponectin receptor2 were differentially methylated independently of the early program. Thus, these analyses identify two types of epigenetic mechanisms that distinguish the pre-set cell fate and later stages of adipose differentiation.

KEYWORDS:

DNA methylation; adipose derived stem cells; epigenetics; fat cells; fat differentiation; induced pluripotent stem cells; reprogramming

PMID:
25093444
PMCID:
PMC4169011
DOI:
10.4161/epi.29856
[Indexed for MEDLINE]
Free PMC Article

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