Histone demethylase KDM4B regulates otic vesicle invagination via epigenetic control of Dlx3 expression

URIBE, R.; BUZZI, A. L.; BRONNER, M.; STROBL-MAZZULLA, P.H.

JOURNAL OF CELL BIOLOGY

ROCKEFELLER UNIV PRESS

Lugar: New York; Año: 2015 vol. 211 p. 815 - 827

0021-9525

In vertebrates, theinner ear arises from the otic placode, a thickened swathe of ectoderm thatinvaginates to form the otic vesicle. We report that histone demethylase KDM4Bis dynamically expressed during early stages of chick inner ear formation. Lossof KDM4B results in defective invagination and striking morphological changesin the otic epithelium, characterized by abnormal localization of adhesion andcytoskeletal molecules and reduced expression of several inner ear markers,including Dlx3. In vivo chromatin immunoprecipitation reveals direct and dynamic occupancyof KDM4B and its target, H3K9me3, at regulatory regions of the Dlx3 locus. Accordingly, co-electroporationsof DLX3 or KDM4B encoding constructs, but not a catalytically dead mutant ofKDM4B, rescue the ear invagination phenotype caused by KDM4B knock-down.Moreover, loss of DLX3 phenocopies loss of KDM4B. Taken together, our findingssuggest that KDM4B play a critical role during inner ear invagination, viamodulating histone methylation of the direct target Dlx3.