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Different CHD chromatin remodelers are required for expression of distinct gene sets and specific stages during development of Dictyostelium discoideum

Platt, James Louis, Rogers, Benjamin James, Rogers, Kelley C., Harwood, Adrian John and Kimmel, Alan R. 2013. Different CHD chromatin remodelers are required for expression of distinct gene sets and specific stages during development of Dictyostelium discoideum. Development 140 (24) , pp. 4926-4936. 10.1242/dev.099879

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Abstract

Control of chromatin structure is crucial for multicellular development and regulation of cell differentiation. The CHD (chromodomain-helicase-DNA binding) protein family is one of the major ATP-dependent, chromatin remodeling factors that regulate nucleosome positioning and access of transcription factors and RNA polymerase to the eukaryotic genome. There are three mammalian CHD subfamilies and their impaired functions are associated with several human diseases. Here, we identify three CHD orthologs (ChdA, ChdB and ChdC) in Dictyostelium discoideum. These CHDs are expressed throughout development, but with unique patterns. Null mutants lacking each CHD have distinct phenotypes that reflect their expression patterns and suggest functional specificity. Accordingly, using genome-wide (RNA-seq) transcriptome profiling for each null strain, we show that the different CHDs regulate distinct gene sets during both growth and development. ChdC is an apparent ortholog of the mammalian Class III CHD group that is associated with the human CHARGE syndrome, and GO analyses of aberrant gene expression in chdC nulls suggest defects in both cell-autonomous and non-autonomous signaling, which have been confirmed through analyses of chdC nulls developed in pure populations or with low levels of wild-type cells. This study provides novel insight into the broad function of CHDs in the regulation development and disease, through chromatin-mediated changes in directed gene expression.

Item Type: Article
Status: Published
Schools: Biosciences
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: Q Science > Q Science (General)
Uncontrolled Keywords: SNF2; Transcriptome profiling; RNA-seq; Chemotaxis; Growth; Differentiation
Publisher: The Company of Biologists
ISSN: 0950-1991
Funders: Wellcome Trust
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Jun 2017 05:50
URI: http://orca.cf.ac.uk/id/eprint/53971

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