HNF4α is required for Tkfc promoter activation by ChREBP.
Biosci Biotechnol Biochem
; 88(8): 941-947, 2024 Jul 22.
Article
in En
| MEDLINE
| ID: mdl-38782732
ABSTRACT
Triokinase/FMN cyclase (Tkfc) is involved in fructose metabolism and is responsible for the phosphorylation of glyceraldehyde to glyceraldehyde-3-phosphate. In this study, we showed that refeeding induced hepatic expression of Tkfc in mice. Luciferase reporter gene assays using the Tkfc promoter revealed the existence of 2 hepatocyte nuclear factor 4α (HNF4α)-responsive elements (HNF4RE1 and HNF4RE2) and 1 carbohydrate-responsive element-binding protein (ChREBP)-responsive element (ChoRE1). Deletion and mutation of HNF4RE1 and HNF4RE2 or ChoRE1 abolished HNF4α and ChREBP responsiveness, respectively. HNF4α and ChREBP synergistically stimulated Tkfc promoter activity. ChoRE1 mutation attenuated but maintained HNF4α responsiveness, whereas HNF4RE1 and HNF4RE2 mutations abolished ChREBP responsiveness. Moreover, Tkfc promoter activity stimulation by ChREBP was attenuated upon HNF4α knockdown. Furthermore, Tkfc expression was decreased in the livers of ChREBP-/- and liver-specific HNF4-/- (Hnf4αΔHep) mice. Altogether, our data indicate that Tkfc is a target gene of ChREBP and HNF4α, and Tkfc promoter activity stimulation by ChREBP requires HNF4α.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Promoter Regions, Genetic
/
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
/
Hepatocyte Nuclear Factor 4
/
Liver
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Biosci Biotechnol Biochem
Journal subject:
BIOQUIMICA
/
BIOTECNOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Japón