Sox2 function as a negative regulator to control HAMP expression
Biol. Res
; 48: 1-8, 2015. graf
Article
em En
| LILACS
| ID: biblio-950787
Biblioteca responsável:
CL1.1
ABSTRACT
BACKGROUND:
Hepcidin, encoding by HAMP gene, is the pivotal regulator of iron metabolism, controlling the systemic absorption and transportation of irons from intracellular stores. Abnormal levels of HAMP expression alter plasma iron parameters and lead to iron metabolism disorders. Therefore,itis animportant goal to understand the mechanisms controlling HAMP gene expression.RESULTS:
Overexpression of Sox2 decrease basal expression of HAMP or induced by IL-6 or BMP-2, whereas, knockdown of Sox2 can increase HAMP expression, furthermore, two potential Sox2-binding sites were identified within the human HAMP promoter. Indeed, luciferase experiments demonstrated that deletion of any Sox2-binding site impaired the negative regulation of Sox2 on HAMP promoter transcriptional activity in basal conditions. ChIP experiments showed that Sox2 could directly bind to these sites. Finally, we verified the role of Sox2 to negatively regulate HAMP expression in human primary hepatocytes.CONCLUSION:
We found that Sox2 as a novel factor to bind with HAMP promoter to negatively regulate HAMP expression, which may be further implicated as a therapeutic option for the amelioration of HAMP-overexpression-related diseases, including iron deficiency anemia.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
LILACS
Assunto principal:
Regulação Neoplásica da Expressão Gênica
/
Hepatócitos
/
Fatores de Transcrição SOXB1
/
Hepcidinas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Biol. Res
Ano de publicação:
2015
Tipo de documento:
Article