Krüppel-like factor-10 is directly regulated by carbohydrate response element-binding protein in rat primary hepatocytes

Katsumi Iizuka, Jun Takeda, Yukio Horikawa

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)638-643
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume412
Issue number4
DOIs
Publication statusPublished - 09-09-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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