Regulation of nucleosome positioning by a CHD Type III chromatin remodeler and its relationship to developmental gene expression inDictyostelium.
Nucleosome placement and repositioning can direct transcription of individual genes; however, the precise interactions of these events are complex and largely unresolved at the whole-genome level. The Chromodomain-Helicase-DNA binding (CHD) Type III proteins are a subfamily of SWI2/SNF2 proteins that control nucleosome positioning and are associated with several complex human disorders, including CHARGE syndrome and autism. Type III CHDs are required for multicellular development of animals andDictyosteliumbut are absent in plants and yeast. These CHDs can mediate nucleosome translocation in vitro, but their in vivo mechanism is unknown. Here, we use genome-wide analysis of nucleosome positioning and transcription profiling to investigate the in vivo relationship between nucleosome positioning and gene expression during development of wild-type (WT)Dictyosteliumand mutant cells lacking ChdC, a Type III CHD protein ortholog. We demonstrate major nucleosome positional changes associated with developmental gene regulation in WT. Loss ofchdCcaused an increase of intragenic nucleosome spacing and misregulation of gene expression, affecting ∼50% of the genes that are repositioned during WT development. These analyses demonstrate active nucleosome repositioning duringDictyosteliummulticellular development, establish an in vivo function of CHD Type III chromatin remodeling proteins in this process, and reveal the detailed relationship between nucleosome positioning and gene regulation, as cells transition between developmental states.
School of Biosciences, Cardiff University, Cardiff, CF10 3AX, United Kingdom.|Laboratory of Cellular and Developmental Biology, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
James L
JL
Platt
School of Biosciences, Cardiff University, Cardiff, CF10 3AX, United Kingdom.
Nicholas A
NA
Kent
Laboratory of Cellular and Developmental Biology, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Alan R
AR
Kimmel
School of Biosciences, Cardiff University, Cardiff, CF10 3AX, United Kingdom.|Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, CF24 4HQ, United Kingdom.
Adrian J
0000-0003-3124-5169
AJ
Harwood
D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000378:metabolism*; D004023:Dictyostelium / Q000235:genetics / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism*; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism*
D009707:Nucleosomes; D015800:Protozoan Proteins; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D004265:DNA Helicases