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| 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
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| 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.
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| 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.
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| 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 |
| E-mail(s) |
albert.basson@kcl.ac.uk
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| Organization name |
King's College London
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| Department |
Craniofacial Development and Stem Cell Biology
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| Street address |
Floor 27, Tower Wing, Guy's Hospital
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| City |
London |
| ZIP/Postal code |
SE19RT |
| Country |
United Kingdom |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA354712 |
| SRA |
SRP093826 |
| 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 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
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