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Status |
Public on Jun 15, 2019 |
Title |
Mapping cis-regulatory chromatin contacts in neural cells links neuropsychiatric disorder risk variants to target genes [CUT&RUN] |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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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.
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Overall design |
H3K27ac and CTCF CUT&RUN on iPSC-induced excitatory neurons (1 replicates) and iPSC-induced lower motor neurons (2 replicates)
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Contributor(s) |
Song M, Shen Y |
Citation(s) |
31367015 |
Submission date |
Feb 07, 2019 |
Last update date |
Apr 08, 2021 |
Contact name |
Yin Shen |
E-mail(s) |
Yin.Shen@ucsf.edu
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Phone |
4155023403
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Organization name |
UCSF
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Department |
Department of Neurology
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Lab |
Shen Lab
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Street address |
513 Parnassus Ave
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City |
SAN FRANCISCO |
State/province |
CALIFORNIA |
ZIP/Postal code |
94143-0410 |
Country |
USA |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (6)
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GSM3593769 |
CUT&RUN-H3K27ac_iPSC-induced lower motor neurons_rep1 |
GSM3593770 |
CUT&RUN-CTCF_iPSC-induced lower motor neurons_rep1 |
GSM3593771 |
CUT&RUN-H3K27ac_iPSC-induced lower motor neurons_rep2 |
GSM3593772 |
CUT&RUN-H3K27ac_iPSC-induced excitatory neurons_rep1 |
GSM3593773 |
CUT&RUN-CTCF_iPSC-induced lower motor neurons_rep2 |
GSM3593774 |
CUT&RUN-CTCF_iPSC-induced excitatory neurons_rep1 |
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This SubSeries is part of SuperSeries: |
GSE113483 |
Mapping cis-regulatory chromatin contacts in neural cells links neuropsychiatric disorder risk variants to target genes |
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Relations |
BioProject |
PRJNA521322 |
SRA |
SRP184484 |
Supplementary file |
Size |
Download |
File type/resource |
GSE126211_IJ195.hg19.bowtie2.bw |
485.0 Mb |
(ftp)(http) |
BW |
GSE126211_IJ195.hg19.nuc.nodups.0.05_peaks.narrowPeak.gz |
1.3 Mb |
(ftp)(http) |
NARROWPEAK |
GSE126211_IJ196.hg19.bowtie2.bw |
191.8 Mb |
(ftp)(http) |
BW |
GSE126211_IJ196.hg19.nuc.nodups.0.05_peaks.narrowPeak.gz |
406.6 Kb |
(ftp)(http) |
NARROWPEAK |
GSE126211_MN.CTCF.merged.0.05_peaks.narrowPeak.gz |
1.0 Mb |
(ftp)(http) |
NARROWPEAK |
GSE126211_MN.CTCF.merged.hg19.bw |
407.3 Mb |
(ftp)(http) |
BW |
GSE126211_MN.H3K27ac.merged.0.05_peaks.narrowPeak.gz |
1.9 Mb |
(ftp)(http) |
NARROWPEAK |
GSE126211_MN.H3K27ac.merged.hg19.bw |
516.7 Mb |
(ftp)(http) |
BW |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |