title: Histone demethylase KDM4B regulates otic vesicle invagination via epigenetic control of Dlx3 expression.
abstract: 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.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Rosa A
authors.initials: RA
authors.lastname: Uribe
authors.affiliation: Laboratory of Developmental Biology, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (CONICET-UNSAM), 7130 Chascomús, Argentina.
authors.forename: Ailín L
authors.initials: AL
authors.lastname: Buzzi
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Bronner
authors.affiliation: Laboratory of Developmental Biology, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (CONICET-UNSAM), 7130 Chascomús, Argentina strobl@intech.gov.ar.
authors.forename: Pablo H
authors.initials: PH
authors.lastname: Strobl-Mazzulla
mesh_terms: D000818:Animals; D017209:Apoptosis; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002642:Chick Embryo; D007758:Ear, Inner / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D044127:Epigenesis, Genetic; D015870:Gene Expression; D006657:Histones; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D056484:Jumonji Domain-Containing Histone Demethylases / Q000502:physiology*; D008745:Methylation; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D030161:Avian Proteins; C088334:Distal-less homeobox proteins; D006657:Histones; D018398:Homeodomain Proteins; D014157:Transcription Factors; D056484:Jumonji Domain-Containing Histone Demethylases