title: Krüppel-like factor-10 is directly regulated by carbohydrate response element-binding protein in rat primary hepatocytes.
abstract: Krüppel-like factor (KLF)-10, is a circadian transcriptional regulator, which links the molecular clock to energy metabolism in the liver. Recently, it was reported that Klf-10 expression is induced by glucose stimulation in mouse hepatocytes. We previously reported that carbohydrate response element-binding protein (ChREBP) plays an important role in the regulation of hepatic lipogenic gene expression. Here, we investigate whether ChREBP, a glucose-activated transcription factor, directly regulates Klf-10 mRNA expression in rat primary hepatocytes. We found that both glucose stimulation and adenoviral overexpression of ChREBP induce Klf-10 mRNA expression in rat primary hepatocytes in a dose-dependent manner. Conversely, overexpression of dominant-negative Max-like protein inhibits glucose-induction expression of Klf-10 mRNA. Deletion analysis using rat Klf-10 promoter in the pGL3 vector combined with a chromatin immunoprecipitation assay against the anti-ChREBP antibody demonstrated that the carbohydrate response element is located between -125 bp and -109 bp in the rat Klf-10 promoter. Conversely, adenoviral overexpression of KLF-10 partly inhibits glucose induction of ChREBP target genes in primary hepatocytes. In conclusion, these data suggest that crosstalk between ChREBP and KLF-10 is involved in the regulation of the lipogenic pathway.
authors.affiliation: Department of Diabetes and Endocrinology, Graduate School of Medicine, Gifu University, Gifu, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Iizuka
authors.forename: Jun
authors.initials: J
authors.lastname: Takeda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Horikawa
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D050155:Lipogenesis / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017208:Rats, Wistar; D020218:Response Elements; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C491385:Klf10 protein, rat; D051741:Kruppel-Like Transcription Factors; C442825:Mlxipl protein, rat; D014157:Transcription Factors; D005947:Glucose