Positional Cloning of the Young Mutation Identifies an Essential Role for the Brahma Chromatin Remodeling Complex in Mediating Retinal Cell Differentiation

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2003 May 16

PMID 12748389

Citations 43

Authors

Ronald G Gregg

Gregory B Willer

James M Fadool

John E Dowling

Brian A Link

Affiliations

Soon will be listed here.

Abstract

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.

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