GEO DataSets

(Submitter supplied) 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. more...

Organism:

Homo sapiens; Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platforms:

GPL17021 GPL16791

26 Samples

Download data: BAM, BED, BW, TXT

(Submitter supplied) We performed a Massively Parallel Reporter Assay (MPRA) to screen >30,000 human-specific substitutions in ChIP-seq-identified Human Gain Enhancers (HGEs) and Human Accelerated Regions (HARs), highly conserved non-coding regions that show accelerated sequence evolution in humans. After comparing human and chimpanzee reference alleles, we used a second MPRA to deconvolute individual substitutions within differentially active enhancers from substitutions in the same fragment and from other variants (human segregating variants or chimpanzee-specific variants) to isolate their specific effects on enhancer activity.

Organism:

Homo sapiens; Pan troglodytes

Type:

Other; Genome binding/occupancy profiling by high throughput sequencing

4 related Platforms

18 Samples

Download data: BIGBED, BW, TSV, TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

27 Samples

Download data: BED

(Submitter supplied) Truncating mutations of CHD8, encoding a chromodomain helicase, and of many other genes with diverse functions, are strong-effect risk factors for autism spectrum disorder (ASD), suggesting multiple mechanisms of pathogenesis. We explored the transcriptional networks that CHD8 regulates in neural progenitor cells (NPCs) by reducing its expression and then integrating transcriptome sequencing (RNA-seq) with genome-wide CHD8 binding (ChIP-seq). more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

22 Samples

Download data: TXT

(Submitter supplied) Truncating mutations of CHD8, encoding a chromodomain helicase, and of many other genes with diverse functions, are strong-effect risk factors for autism spectrum disorder (ASD), suggesting multiple mechanisms of pathogenesis. We explored the transcriptional networks that CHD8 regulates in neural progenitor cells (NPCs) by reducing its expression and then integrating transcriptome sequencing (RNA-seq) with genome-wide CHD8 binding (ChIP-seq). more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

5 Samples

Download data: BED

(Submitter supplied) CHD8 (chromodomain helicase DNA binding protein 8), which codes for a member of the CHD family of ATP-dependent chromatin-remodeling factors, is the most commonly mutated gene in autism spectrum disorders (ASD) identified in exome-sequencing studies. Loss of function mutations in the gene have also been found in schizophrenia (SZ) and intellectual disabilities, and affects cancer cell proliferation. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

6 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

15 Samples

Download data: BED

(Submitter supplied) In this study, we developed two isogenic haploinsufficient CHD8+/– human embryonic stem cell lines (hESCs) that we induced into neurons (iNs) upon doxycycline-inducible overexpression of Neurogenin 2 and Neurogenin 1 (NEUROG2/1), and we profiled the key molecular alterations in chromatin accessibility (ATAC-seq) and expression (RNA-seq) resulting from the loss of CHD8, the most recurrently mutated gene in autism spectrum disorders (ASD).

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

9 Samples

Download data: TXT

(Submitter supplied) In this study, we developed two isogenic haploinsufficient CHD8+/– human embryonic stem cell lines (hESCs) that we induced into neurons (iNs) upon doxycycline-inducible overexpression of Neurogenin 2 and Neurogenin 1 (NEUROG2/1), and we profiled the key molecular alterations in chromatin accessibility (ATAC-seq) and expression (RNA-seq) resulting from the loss of CHD8, the most recurrently mutated gene in autism spectrum disorders (ASD).

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

6 Samples

Download data: BED

(Submitter supplied) Autism spectrum disorder (ASD) is a common and etiologically heterogeneous neurodevelopmental disorder. Although many genetic causes have been identified (>200 ASD-risk genes), no single gene mutation accounts for >1% of all ASD cases. A role for epigenetic mechanisms in ASD etiology is supported by the fact that many ASD-risk genes function as epigenetic regulators and evidence that epigenetic dysregulation can interrupt normal brain development. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL13534

134 Samples

Download data: IDAT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL19057 GPL21103

28 Samples

Download data: BED, BIGWIG, TSV

(Submitter supplied) The chromatin remodeler CHD8 is among the most frequently mutated genes in autism spectrum disorder (ASD). CHD8 has a dosage-sensitive role in ASD but when and how it becomes critical to human social function is unclear. Here, we conducted genomic analyses of heterozygous and homozygous Chd8 mouse embryonic stem cells and differentiated neural progenitors. We identify dosage-sensitive CHD8 transcriptional targets, sites of regulated accessibility, and an unexpected cooperation with SOX transcription factors. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

12 Samples

Download data: TSV

(Submitter supplied) The chromatin remodeler CHD8 is among the most frequently mutated genes in autism spectrum disorder (ASD). CHD8 has a dosage-sensitive role in ASD but when and how it becomes critical to human social function is unclear. Here, we conducted genomic analyses of heterozygous and homozygous Chd8 mouse embryonic stem cells and differentiated neural progenitors. We identify dosage-sensitive CHD8 transcriptional targets, sites of regulated accessibility, and an unexpected cooperation with SOX transcription factors. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL19057

4 Samples

Download data: BED, BIGWIG

(Submitter supplied) The chromatin remodeler CHD8 is among the most frequently mutated genes in autism spectrum disorder (ASD). CHD8 has a dosage-sensitive role in ASD but when and how it becomes critical to human social function is unclear. Here, we conducted genomic analyses of heterozygous and homozygous Chd8 mouse embryonic stem cells and differentiated neural progenitors. We identify dosage-sensitive CHD8 transcriptional targets, sites of regulated accessibility, and an unexpected cooperation with SOX transcription factors. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL21103

12 Samples

Download data: BIGWIG

(Submitter supplied) We examined the impact of germline heterozygous frameshift Chd8 mutation on neurodevelopment in mice. Adult Chd8+/del5 mice exhibited cognitive impairment correlated with increased cerebral cortex, hippocampus, and amygdala volume, but displayed normal social interactions and no repetitive behaviors. Network analysis of neurodevelopmental gene expression revealed widespread transcriptional changes in Chd8+/del5 mice across pathways disrupted in neurodevelopmental disorders, including neurogenesis, synaptic processes, and neuroimmune signaling. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL21103 GPL13112

12 Samples

Download data: BW, NARROWPEAK, TXT

(Submitter supplied) The chromodomain helicase DNA binding protein CHD8 is among the most frequently found de-novo mutations in autism. Unlike other autism-risk genes, CHD8 mutations appear to be fully penetrant. Despite this prominent disease involvement, relatively little is known about its molecular function. Based on sequence homology, CHD8 is believed to be a chromatin regulator but mechanisms for its genomic targeting and its function on chromatin are unclear. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platform:

GPL18573

11 Samples

Download data: TXT, XLSX

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

30 Samples

Download data: BIGWIG, BROADPEAK

(Submitter supplied) Oligodendrocyte precursor cells (OPCs) constitute the main proliferative cells in the adult brain, and deregulation of OPC proliferation-differentiation balance results in either glioma formation or defective adaptive (re)myelination. OPC differentiation requires significant genetic reprogramming implicating chromatin remodeling. Mounting evidence indicates that chromatin remodelers play important roles during normal development and their mutations are associated with neurodevelopmental defects, with CHD7 haploinsuficiency being the cause of CHARGE syndrome and CHD8 being one of the strongest Autism Spectrum Disorder (ASD) high-risk associated genes. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

12 Samples

Download data: XLSX

(Submitter supplied) Oligodendrocyte precursor cells (OPCs) constitute the main proliferative cells in the adult brain, and deregulation of OPC proliferation-differentiation balance results in either glioma formation or defective adaptive (re)myelination. OPC differentiation requires significant genetic reprogramming implicating chromatin remodeling. Mounting evidence indicates that chromatin remodelers play important roles during normal development and their mutations are associated with neurodevelopmental defects, with CHD7 haploinsuficiency being the cause of CHARGE syndrome and CHD8 being one of the strongest Autism Spectrum Disorder (ASD) high-risk associated genes. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

8 Samples

Download data: BROADPEAK, XLSX

(Submitter supplied) Oligodendrocyte precursor cells (OPCs) constitute the main proliferative cells in the adult brain, and deregulation of OPC proliferation-differentiation balance results in either glioma formation or defective adaptive (re)myelination. OPC differentiation requires significant genetic reprogramming implicating chromatin remodeling. Here, we report on uncharacterized functions of the chromatin remodelers Chd7 and Chd8 in OPCs. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

10 Samples

Download data: BIGWIG