The Transcription Factor ATF7 Controls Adipocyte Differentiation and Thermogenic Gene Programming.

The adipocytes functions as a central organ in the regulation of metabolic homeostasis. Factors which contribute to the adipocyte differentiation and function would be the promising targets to combat the obesity and associated metabolic disorders. The activating transcription factor 7 (ATF7), a stress-responsive chromatin regulator, has recently been shown to be involved in the energy metabolism; however, the underlying mechanisms are still unknown. Here, we show that ATF7 is required for adipocyte differentiation and it interacts with histone dimethyltransferase G9a in adipocyte to repress the interferon-stimulated genes (ISGs) expression, which suppresses adipogenesis. Ablation of ATF7 promotes the beige biogenesis and browning of inguinal white adipose tissue (iWAT). ATF7 binds to the transcription regulatory regions of Ucp1 gene, and silences it by maintaining the histone H3K9 dimethylation level. These results establish the multifunction of ATF7 in adipocyte and provide molecular insights into the epigenetic control of development and function of adipose tissues. Overall design: Beige adipocytes derived from WT and ATF7 KO inguinal WAT preadipocytes with rosiglitazone treatment, in duplicate; white adipocytes derived from WT and ATF7 KO inguinal WAT preadipocytes without rosiglitazone treatment, in duplicate; beige adipocytes derived from control and ATF7 overexpressing C3H10t1/2 with rosiglitazone treatment, in duplicate, using NextSeq500 Illumina.

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Liu Y, Maekawa T, Yoshida K, Muratani M, Chatton B, Ishii S