| First Author | Liu Y | Year | 2018 |
| Journal | J Biol Chem | Volume | 293 |
| Issue | 36 | Pages | 14012-14021 |
| PubMed ID | 30026232 | Mgi Jnum | J:271049 |
| Mgi Id | MGI:6223406 | Doi | 10.1074/jbc.RA118.004401 |
| Citation | Liu Y, et al. (2018) Kruppel-like factor 10 (KLF10) is transactivated by the transcription factor C/EBPbeta and involved in early 3T3-L1 preadipocyte differentiation. J Biol Chem 293(36):14012-14021 |
| abstractText | Adipose tissue stores energy and plays an important role in energy homeostasis. CCAAT/enhancer-binding protein beta (C/EBPbeta) is an important early transcription factor for 3T3-L1 preadipocyte differentiation, facilitating mitotic clonal expansion (MCE) and transactivating C/EBPalpha and peroxisome proliferator-activated receptor-gamma (PPARgamma) to promote adipogenesis. C/EBPbeta is induced early, but the expression of antimitotic C/EBPalpha and PPARgamma is not induced until approximately 48 h. The delayed expression of C/EBPalpha and PPARgamma is thought to ensure MCE progression, but the molecular mechanism for this delay remains elusive. Here, we show that the zinc-finger transcription factor Kruppel-like factor 10 (KLF10) is induced after adipogenic induction and that its expression positively correlates with that of C/EBPbeta but inversely correlates with expression of C/EBPalpha and PPARgamma. C/EBPbeta bound to the KLF10 promoter and transactivated its expression during MCE. KLF10 overexpression in 3T3-L1 preadipocyte repressed adipogenesis and decreased C/EBPalpha and PPARgamma expression, whereas siRNA-mediated down-regulation of KLF10 enhanced adipogenesis and increased C/EBPalpha and PPARgamma expression. Luciferase assays revealed an inhibitory effect of KLF10 on C/EBPalpha promoter activity. Using promoter deletion and mutation analysis, we identified a KLF10-binding site within the proximal promoter region of C/EBPalpha. Furthermore, KLF10 interacted with and recruited histone deacetylase 1 (HDAC1) to the C/EBPalpha promoter, decreasing acetylated histone H4 on the C/EBPalpha promoter and inactivating C/EBPalpha transcription. Because C/EBPalpha can transactivate PPARgamma, our results suggest a mechanism by which expression of C/EBPalpha and PPARgamma is delayed via KLF10 expression and shed light on the negative feedback loop for C/EBPbeta-regulated adipogenesis in 3T3-L1 preadipocyte. |
