Methylome, transcriptome, and PPAR gamma cistrome analyses reveal two epigenetic transitions in fat cells

作者：Takada Hitomi; Saito Yutaka; Mituyama Toutai; Wei Zong; Yoshihara Eiji; Jacinto Sandra; Downes Michael; Evans Ronald M; Kida Yasuyuki S^*

来源：Epigenetics, 2014, 9(9): 1195-1206.

DOI：10.4161/epi.29856

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

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 gamma 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 gamma 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 gamma-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.

• 出版日期2014-9