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Series GSE57369 Query DataSets for GSE57369
Status Public on Jan 21, 2015
Title The chromatin modifier CHD8 targets autism risk genes during human neurodevelopment 
Organisms Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Whole-exome sequencing studies have implicated chromatin modifiers and transcriptional regulators in autism spectrum disorder (ASD) through the identification of de novo loss of function mutations in affected individuals. Many of these genes are co-expressed in mid-fetal human cortex, suggesting ASD risk genes converge in regulatory networks that are perturbed in ASD during neurodevelopment. To elucidate such networks we mapped promoters and enhancers bound by the chromodomain helicase CHD8, which is strongly enriched in ASD-associated de novo loss of function mutations, using ChIP-seq in mid-fetal human brain, human neural stem cells (hNSCs), and embryonic mouse cortex. We find that CHD8 targets are strongly enriched for ASD risk genes that converge in ASD-associated co-expression networks in human midfetal cortex. CHD8 knockdown in hNSCs results in significant dysregulation of ASD risk genes targeted by CHD8, as well as additional genes important for neurodevelopment, including members of the Wnt/β-catenin signaling pathway. Integration of CHD8 binding data with genetic and gene co-expression data in ASD risk models provides support for additional ASD risk genes. Together, our results suggest that loss of CHD8 function contributes to ASD through regulatory perturbation of other ASD risk genes during human cortical development.
 
Overall design Two biological replicates for each ChIP with appropriate Input control
Four biological replicates for each condition in knockdown experiments (Ctrl construct, Chd8 target C, and Chd8 target G)

No raw data are provided for human samples (GSM1381214-GSM1381221) due to patient confidentiality issue. Human alignments were anonymized by removing sequence information and provided as aligned bam files instead
 
Contributor(s) Cotney J, Noonan JP
Citation(s) 25752243
Submission date May 07, 2014
Last update date May 15, 2019
Contact name Justin Cotney
E-mail(s) cotney@uchc.edu
Organization name UConn Health
Department Genetics and Genome Sciences
Lab Cotney Lab
Street address 400 Farmington Ave.
City Farmington
State/province CT
ZIP/Postal code 06030-6403
Country USA
 
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (26)
GSM1381214 141_CBC_Chd8
GSM1381215 141_DFC_Chd8
GSM1381216 141_Striatum_Chd8
Relations
BioProject PRJNA246355
SRA SRP041738

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
GSE57369_RAW.tar 29.5 Gb (http)(custom) TAR (of BAM, BED, BW, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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