Krüppel-like factor 10 (KLF10) is transactivated by the transcription factor C/EBPβ and involved in early 3T3-L1 preadipocyte differentiation

Yuan Liu, Wan-Qiu Peng, Ying-Ying Guo, Yang Liu, Qi-Qun Tang, Liang Guo
2018 Journal of Biological Chemistry  
Edited by Jeffrey E. Pessin Adipose tissue stores energy and plays an important role in energy homeostasis. CCAAT/enhancer-binding protein ␤ (C/EBP␤) is an important early transcription factor for 3T3-L1 preadipocyte differentiation, facilitating mitotic clonal expansion (MCE) and transactivating C/EBP␣ and peroxisome proliferator-activated receptor-␥ (PPAR␥) to promote adipogenesis. C/EBP␤ is induced early, but the expression of antimitotic C/EBP␣ and PPAR␥ is not induced until ϳ48 h. The
more » ... ed expression of C/EBP␣ and PPAR␥ is thought to ensure MCE progression, but the molecular mechanism for this delay remains elusive. Here, we show that the zinc-finger transcription factor Krüppel-like factor 10 (KLF10) is induced after adipogenic induction and that its expression positively correlates with that of C/EBP␤ but inversely correlates with expression of C/EBP␣ and PPAR␥. C/EBP␤ bound to the KLF10 promoter and transactivated its expression during MCE. KLF10 overexpression in 3T3-L1 preadipocyte repressed adipogenesis and decreased C/EBP␣ and PPAR␥ expression, whereas siRNAmediated down-regulation of KLF10 enhanced adipogenesis and increased C/EBP␣ and PPAR␥ expression. Luciferase assays revealed an inhibitory effect of KLF10 on C/EBP␣ promoter activity. Using promoter deletion and mutation analysis, we identified a KLF10-binding site within the proximal promoter region of C/EBP␣. Furthermore, KLF10 interacted with and recruited histone deacetylase 1 (HDAC1) to the C/EBP␣ promoter, decreasing acetylated histone H4 on the C/EBP␣ promoter and inactivating C/EBP␣ transcription. Because C/EBP␣ can transactivate PPAR␥, our results suggest a mechanism by which expression of C/EBP␣ and PPAR␥ is delayed via KLF10 expression and shed light on the negative feedback loop for C/EBP␤-regulated adipogenesis in 3T3-L1 preadipocyte.
doi:10.1074/jbc.ra118.004401 pmid:30026232 fatcat:o7mdfpo64vg35davrkbiaehd6a