Suppression of gluconeogenic gene expression by LSD1-mediated histone demethylation.
PLoS One
; 8(6): e66294, 2013.
Article
en En
| MEDLINE
| ID: mdl-23755305
ABSTRACT
Aberrant gluconeogenic gene expression is associated with diabetes, glycogen storage disease, and liver cancer. However, little is known how these genes are regulated at the chromatin level. In this study, we investigated in HepG2 cells whether histone demethylation is a potential mechanism. We found that knockdown or pharmacological inhibition of histone demethylase LSD1 causes remarkable transcription activation of two gluconeogenic genes, FBP1 and G6Pase, and consequently leads to increased de novo glucose synthesis and decreased intracellular glycogen content. Mechanistically, LSD1 occupies the promoters of FBP1 and G6Pase, and modulates their H3K4 dimethylation levels. Thus, our work identifies an epigenetic pathway directly governing gluconeogenic gene expression, which might have important implications in metabolic physiology and diseases.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Histonas
/
Procesamiento Proteico-Postraduccional
/
ADN Helicasas
/
Glucosa-6-Fosfatasa
/
Epigénesis Genética
/
Proteínas de Unión al ADN
/
Histona Demetilasas
Límite:
Humans
Idioma:
En
Año:
2013
Tipo del documento:
Article