Artículos de revistas
Histone demethylase KDM4B regulates otic vesicle invagination via epigenetic control of Dlx3 expression
Fecha
2015-11Registro en:
Uribe, Rosa A.; Buzzi, Ailín Leticia; Bronner, Marianne E.; Strobl Mazulla, Pablo Hernan; Histone demethylase KDM4B regulates otic vesicle invagination via epigenetic control of Dlx3 expression; Rockefeller University Press; Journal of Cell Biology; 211; 4; 11-2015; 815-827
0021-9525
CONICET Digital
CONICET
Autor
Uribe, Rosa A.
Buzzi, Ailín Leticia
Bronner, Marianne E.
Strobl Mazulla, Pablo Hernan
Resumen
In vertebrates, the inner ear arises from the otic placode, a thickened swathe of ectoderm that invaginates to form the otic vesicle. We report that histone demethylase KDM4B is dynamically expressed during early stages of chick inner ear formation. A loss of KDM4B results in defective invagination and striking morphological changes in the otic epithelium, characterized by abnormal localization of adhesion and cytoskeletal molecules and reduced expression of several inner ear markers, including Dlx3. In vivo chromatin immunoprecipitation reveals direct and dynamic occupancy of KDM4B and its target, H3K9me3, at regulatory regions of the Dlx3 locus. Accordingly, coelectroporations of DLX3 or KDM4B encoding constructs, but not a catalytically dead mutant of KDM4B, rescue the ear invagination phenotype caused by KDM4B knockdown. Moreover, a loss of DLX3 phenocopies a loss of KDM4B. Collectively, our findings suggest that KDM4B play a critical role during inner ear invagination via modulating histone methylation of the direct target Dlx3.