Interplay between HDAC3 and WDR5 is essential for hypoxia-induced epithelial-mesenchymal transition.
Mol Cell
; 43(5): 811-22, 2011 Sep 02.
Article
em En
| MEDLINE
| ID: mdl-21884981
ABSTRACT
Epithelial-mesenchymal transition (EMT) is important for organ development, metastasis, cancer stemness, and organ fibrosis. Molecular mechanisms to coordinately regulate hypoxia-induced EMT remain elusive. Here, we show that HIF-1α-induced histone deacetylase 3 (hdac3) is essential for hypoxia-induced EMT and metastatic phenotypes. Change of specific chromatin states is associated with hypoxia-induced EMT. Under hypoxia, HDAC3 interacts with hypoxia-induced WDR5, recruits the histone methyltransferase (HMT) complex to increase histone H3 lysine 4 (H3K4)-specific HMT activity, and activates mesenchymal gene expression. HDAC3 also serves as an essential corepressor to repress epithelial gene expression. Knockdown of WDR5 abolishes mesenchymal gene activation but not epithelial gene repression during hypoxia. These results indicate that hypoxia induces different chromatin modifiers to coordinately regulate EMT through distinct mechanisms.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Histona-Lisina N-Metiltransferase
/
Transição Epitelial-Mesenquimal
/
Histona Desacetilases
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article