Epigenetic programming of Dnmt3a mediated by AP2 alpha is required for granting preadipocyte the ability to differentiate

doi:10.1038/cddis.2016.378

	Epigenetic programming of Dnmt3a mediated by AP2 alpha is required for granting preadipocyte the ability to differentiate
	Guo, Wei 1; Chen, Jiangnan1,2,3 ; Yang, Ying 1; Zhu, Jianbei 1; Wu, Jiarui1,2,4
	2016-12
发表期刊	CELL DEATH & DISEASE
ISSN	2041-4889
卷号	7
发表状态	已发表
DOI	10.1038/cddis.2016.378
摘要	Adipogenesis has an important role in regulating energy homeostasis in mammals. 3T3-L1 preadipocytes have been widely used as an in vitro model for analyzing the molecular mechanism of adipogenesis. Previous reports indicated that the stage of contact inhibition (CI), through which the proliferating cells exit from the cell cycle, was required for granting preadipocyte the ability to differentiate. While this kind of the granting mechanism remains elusive. In the present study, we showed that DNA (cytosine-5) methyltransferase 3a (Dnmt3a) was upregulated at both the mRNA and protein level during the CI stage, and resulted in increasing promoter methylation of adipogenic genes. We further identified that the expression of Activator protein 2 alpha (AP2 alpha), a member of the transcription factor activator protein 2 (AP2) family, was highly correlated with the expression of Dnmt3a during the CI stage. In addition, we showed that AP2 alpha transcriptionally upregulated Dnmt3a by directly binding to its proximal promoter region. Importantly, treatment of 3T3-L1 preadipocytes with AP2 alpha-specific siRNAs inhibited the preadipocyte differentiation in a stagedependent manner, supporting the conclusion that AP2 alpha has an important role during the CI stage. Furthermore, overexpression of Dnmt3a partially rescued the impairment of adipogenesis induced by AP2 alpha knockdown. Collectively, our findings reveal that AP2 alpha is an essential regulator for granting preadipocyte the ability to differentiate through the upregulation of Dnmt3a expression during the CI stage.
收录类别	SCI
语种	英语
资助项目	Natural Science Foundation of Shanghai[15ZR1445900]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000391815800009
出版者	NATURE PUBLISHING GROUP
WOS关键词	MITOTIC CLONAL EXPANSION ; C/EBP-ALPHA EXPRESSION ; TRANSCRIPTION FACTORS ; ADIPOCYTE DIFFERENTIATION ; HISTONE METHYLATION ; ADIPOSE-TISSUE ; PPAR-GAMMA ; ADIPOGENESIS ; GENE ; FAT
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1627
专题	生命科学与技术学院_硕士生生命科学与技术学院
通讯作者	Wu, Jiarui
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Syst Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 3.Univ Chinese Acad Sci, Sch Life Sci, Shanghai, Peoples R China 4.Chinese Acad Sci, Shanghai Adv Res Inst, Shanghai, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Guo, Wei,Chen, Jiangnan,Yang, Ying,et al. Epigenetic programming of Dnmt3a mediated by AP2 alpha is required for granting preadipocyte the ability to differentiate[J]. CELL DEATH & DISEASE,2016,7.
APA	Guo, Wei,Chen, Jiangnan,Yang, Ying,Zhu, Jianbei,&Wu, Jiarui.(2016).Epigenetic programming of Dnmt3a mediated by AP2 alpha is required for granting preadipocyte the ability to differentiate.CELL DEATH & DISEASE,7.
MLA	Guo, Wei,et al."Epigenetic programming of Dnmt3a mediated by AP2 alpha is required for granting preadipocyte the ability to differentiate".CELL DEATH & DISEASE 7(2016).