|
| Status |
Public on Jun 15, 2019 |
| Title |
Mapping cis-regulatory chromatin contacts in neural cells links neuropsychiatric disorder risk variants to target genes [ATAC-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Mutations in gene regulatory elements have been associated with a wide range of complex neuropsychiatric disorders. However, due to their cell-type specificity and difficulties in characterizing their regulatory targets, the ability to identify causal genetic variants has remained limited. To address these constraints, we perform an integrative analysis of chromatin interactions, open chromatin regions and transcriptomes using promoter capture Hi-C, assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing, respectively, in four functionally distinct neural cell types: induced pluripotent stem cell (iPSC)-induced excitatory neurons and lower motor neurons, iPSC-derived hippocampal dentate gyrus-like neurons and primary astrocytes. We identify hundreds of thousands of long-range cis-interactions between promoters and distal promoter-interacting regions, enabling us to link regulatory elements to their target genes and reveal putative processes that are dysregulated in disease. Finally, we validate several promoter-interacting regions by using clustered regularly interspaced short palindromic repeats (CRISPR) techniques in human excitatory neurons, demonstrating that CDK5RAP3, STRAP and DRD2 are transcriptionally regulated by physically linked enhancers.
|
| |
|
| Overall design |
ATAC-seq on iPSC-induced excitatory neurons (2 replicates), iPSC-derived hippocampal dentate gyrus (DG)-like neurons (2 replicates), iPSC-induced lower motor neurons (3 replicates), and human primary fetal astrocytes (4 replicates)
|
| |
|
| Contributor(s) |
Song M, Shen Y |
| Citation(s) |
31367015 |
| |
| Submission date |
Apr 20, 2018 |
| Last update date |
Sep 04, 2019 |
| Contact name |
Yin Shen |
| E-mail(s) |
[email protected]
|
| Phone |
4155023403
|
| Organization name |
UCSF
|
| Department |
Department of Neurology
|
| Lab |
Shen Lab
|
| Street address |
513 Parnassus Ave
|
| City |
SAN FRANCISCO |
| State/province |
CALIFORNIA |
| ZIP/Postal code |
94143-0410 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (11)
|
| GSM3106826 |
ATAC-seq_iPSC-induced excitatory neurons_rep1 |
| GSM3106827 |
ATAC-seq_iPSC-induced excitatory neurons_rep2 |
| GSM3106830 |
ATAC-seq_human primary fetal astrocytes_rep1 |
| GSM3106831 |
ATAC-seq_human primary fetal astrocytes_rep2 |
| GSM3597641 |
ATAC-seq_iPSC-derived hippocampal DG-like neurons_rep1 |
| GSM3597642 |
ATAC-seq_iPSC-derived hippocampal DG-like neurons_rep2 |
| GSM3597643 |
ATAC-seq_iPSC-induced lower motor neurons_rep1 |
| GSM3597644 |
ATAC-seq_iPSC-induced lower motor neurons_rep2 |
| GSM3597645 |
ATAC-seq_iPSC-induced lower motor neurons_rep3 |
| GSM3597646 |
ATAC-seq_human primary fetal astrocytes batch 2_rep1 |
| GSM3597647 |
ATAC-seq_human primary fetal astrocytes batch 2_rep2 |
|
| This SubSeries is part of SuperSeries: |
| GSE113483 |
Mapping cis-regulatory chromatin contacts in neural cells links neuropsychiatric disorder risk variants to target genes |
|
| Relations |
| BioProject |
PRJNA451217 |
| SRA |
SRP141472 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE113480_astrocyte.atac-seq.bigwig |
972.4 Mb |
(ftp)(http) |
BIGWIG |
| GSE113480_astrocyte.atac.seq.narrowPeak.gz |
2.8 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE113480_cortical.atac-seq.bigwig |
829.7 Mb |
(ftp)(http) |
BIGWIG |
| GSE113480_cortical.atac.seq.narrowPeak.gz |
3.3 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE113480_hippocampal.atac-seq.bigwig |
1.0 Gb |
(ftp)(http) |
BIGWIG |
| GSE113480_hippocampal.atac.seq.narrowPeak.gz |
2.8 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE113480_motor.atac-seq.bigwig |
1024.0 Mb |
(ftp)(http) |
BIGWIG |
| GSE113480_motor.atac.seq.narrowPeak.gz |
2.4 Mb |
(ftp)(http) |
NARROWPEAK |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
Less...
More...