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Series GSE90466 Query DataSets for GSE90466
Status Public on Jan 01, 2017
Title CHD7 controls cerebellar development via Reelin
Organism Mus musculus
Experiment type Other
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Mutation of the gene encoding the ATP-dependent chromatin remodeler CHD7 causes CHARGE syndrome. The mechanisms underlying the neurodevelopmental deficits associated with the syndrome, which include cerebellar hypoplasia, developmental delay, coordination problems and autistic features, are not known. CHD7 is expressed in neural stem and progenitor cells, but its role in neurogenesis during brain development remains unknown. Here we show that deletion of Chd7 from cerebellar granule cell precursors (GCps) in the mouse results in reduced GCp proliferation, cerebellar hypoplasia, developmental delay and motor deficits. Genome-wide expression profiling revealed downregulated Reln gene expression in Chd7-deficient GCps. Recessive RELN mutations is associated with severe cerebellar hypoplasia in humans. We provide molecular and genetic evidence that reduced Reln expression contributes substantially to the GCp proliferative defect and cerebellar hypoplasia in GCp-specific Chd7 mouse mutants. Finally, we show that CHD7 is necessary for the maintenance of an open, accessible chromatin state at the Reln locus. Taken together, this study shows that Reln gene expression is regulated by chromatin remodeling, identifies CHD7 as a previously unrecognized upstream regulator of Reln and provides the first evidence that a mammalian CHD protein controls brain development by modulating chromatin accessibility in neuronal progenitors in vivo.
Overall design Examination of the chromatin profile by ATACseq in 3 replicates of control and 3 replicates of Chd7-deficient cerebellar granule cell precurosers (GCps).
Examination of the mRNA profile by RNA-seq in 2 replicates of control and 2 replicates of Chd7-deficient cerebellar granule cell precurosers (GCps).
Investigation of H3K4me1 binding events throughout the genome by ChIP-seq of Control cells.
Contributor(s) Whittaker DE, Riegman KL, Kasah S, Mohan C, Yu T, Sala BP, Hebaishi H, Caruso A, Marques AC, Michetti C, Smachetti ME, Shah A, Sabbioni M, Kulhanci O, Tee W, Reinberg D, Scattoni ML, Volk H, McGonnell I, Wardle F, Fernandes C, Basson MA
Citation(s) 28165338
Submission date Nov 23, 2016
Last update date Oct 21, 2020
Contact name Albert Basson
Organization name King's College London
Department Craniofacial Development and Stem Cell Biology
Street address Floor 27, Tower Wing, Guy's Hospital
City London
ZIP/Postal code SE19RT
Country United Kingdom
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (11)
GSM2401614 WT 1_ATAC
GSM2401615 WT 2_ATAC
GSM2401616 WT 3_ATAC
BioProject PRJNA354712
SRA SRP093826

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE90466_DEGs_Chd7.xls.gz 44.5 Kb (ftp)(http) XLS
GSE90466_KO_R1_htseq_strict_a3_s_counts.txt.gz 152.3 Kb (ftp)(http) TXT
GSE90466_KO_R2_htseq_strict_a3_s_counts.txt.gz 150.7 Kb (ftp)(http) TXT
GSE90466_RAW.tar 97.1 Mb (http)(custom) TAR (of BW)
GSE90466_WT_R1_htseq_strict_a3_s_counts.txt.gz 152.3 Kb (ftp)(http) TXT
GSE90466_WT_R2_htseq_strict_a3_s_counts.txt.gz 150.7 Kb (ftp)(http) TXT
GSE90466_master_sheet_atac_all_datav2.xlsx 5.6 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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