Positional cloning of the young mutation identifies an essential role for the Brahma chromatin remodeling complex in mediating retinal cell differentiation.
Zebrafish with the young (yng) mutation show a defect in retinal cell differentiation. Here we demonstrate that a mutation in a brahma-related gene (brg1) is responsible for the yng phenotype. Brahma homologues function as essential subunits for SWI/SNF-type chromatin remodeling complexes. Our analysis indicates that brg1 is required for the wave of mitogen-activated protein kinase activity that precedes retinal cell differentiation. Using specific inhibitors of the mitogen-activated protein kinase pathway we show this signal has a direct role in retinal cell differentiation. Lastly, through investigations of mutants in other chromatin remodeling subunits, we provide genetic evidence for gene and tissue specificity of the Brahma chromatin remodeling complex.
Department of Biochemistry and Molecular Biology, University of Louisville, 319 Abraham Flexner Way, KY 40202, USA.
Ronald G
RG
Gregg
Gregory B
GB
Willer
James M
JM
Fadool
John E
JE
Dowling
Brian A
BA
Link
D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D002843:Chromatin / Q000378:metabolism*; D003001:Cloning, Molecular; D017931:DNA Primers; D029721:Drosophila Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D015534:Trans-Activators / Q000235:genetics*; D015027:Zebrafish / Q000196:embryology
D018797:Cell Cycle Proteins; D002843:Chromatin; D017931:DNA Primers; D029721:Drosophila Proteins; D015534:Trans-Activators; C086469:brm protein, Drosophila