Insulin represses phosphoenolpyruvate carboxykinase gene transcription by causing the rapid disruption of an active transcription complex: a potential epigenetic effect.
Mol Endocrinol
; 21(2): 550-63, 2007 Feb.
Article
em En
| MEDLINE
| ID: mdl-17095578
ABSTRACT
Insulin represses gluconeogenesis, in part, by inhibiting the transcription of genes that encode rate-determining enzymes, such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase). Glucocorticoids stimulate expression of the PEPCK gene but the repressive action of insulin is dominant. Here, we show that treatment of H4IIE hepatoma cells with the synthetic glucocorticoid, dexamethasone (dex), induces the accumulation of glucocorticoid receptor, as well as many transcription factors, coregulators, and RNA polymerase II, on the PEPCK gene promoter. The addition of insulin to dex-treated cells causes the rapid dissociation of glucocorticoid receptor, polymerase II, and several key transcriptional regulators from the PEPCK gene promoter. These changes are temporally related to the reduced rate of PEPCK gene transcription. A similar disruption of the G-6-Pase gene transcription complex was observed. Additionally, insulin causes the rapid demethylation of arginine-17 on histone H3 of both genes. This rapid, insulin-induced, histone demethylation is temporally related to the disruption of the PEPCK and G-6-Pase gene transcription complex, and may be causally related to the mechanism by which insulin represses transcription of these genes.
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Base de dados:
MEDLINE
Assunto principal:
Fosfoenolpiruvato Carboxiquinase (GTP)
/
Fatores de Transcrição
/
Epigênese Genética
/
Insulina
Limite:
Animals
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article