HCF-1 Regulates De Novo Lipogenesis through a Nutrient-Sensitive Complex with ChREBP.
Mol Cell
; 75(2): 357-371.e7, 2019 07 25.
Article
in En
| MEDLINE
| ID: mdl-31227231
ABSTRACT
Carbohydrate response element binding protein (ChREBP) is a key transcriptional regulator of de novo lipogenesis (DNL) in response to carbohydrates and in hepatic steatosis. Mechanisms underlying nutrient modulation of ChREBP are under active investigation. Here we identify host cell factor 1 (HCF-1) as a previously unknown ChREBP-interacting protein that is enriched in liver biopsies of nonalcoholic steatohepatitis (NASH) patients. Biochemical and genetic studies show that HCF-1 is O-GlcNAcylated in response to glucose as a prerequisite for its binding to ChREBP and subsequent recruitment of OGT, ChREBP O-GlcNAcylation, and activation. The HCF-1ChREBP complex resides at lipogenic gene promoters, where HCF-1 regulates H3K4 trimethylation to prime recruitment of the Jumonji C domain-containing histone demethylase PHF2 for epigenetic activation of these promoters. Overall, these findings define HCF-1's interaction with ChREBP as a previously unappreciated mechanism whereby glucose signals are both relayed to ChREBP and transmitted for epigenetic regulation of lipogenic genes.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Homeodomain Proteins
/
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
/
Host Cell Factor C1
/
Lipogenesis
/
Non-alcoholic Fatty Liver Disease
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2019
Type:
Article
Affiliation country:
United States