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Series GSE111170 Query DataSets for GSE111170
Status Public on Aug 29, 2018
Title Short tandem repeats susceptible to pathogenic instability linked to chromatin domain disruption
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary More than 25 inherited human disorders are caused by the unstable expansion of repetitive DNA sequences termed short tandem repeats (STRs). A fundamental unresolved question is why some STRs are susceptible to pathologic expansion, whereas thousands of repeat tracts across the human genome are relatively stable. Here, we discover that nearly all disease-associated STRs (daSTRs) are located at boundaries demarcating 3D chromatin domains. We identify a subset of boundaries with markedly higher CpG island density compared to the rest of the genome. daSTRs specifically localize to ultra-high-density CpG island boundaries, suggesting they might be hotspots for epigenetic misregulation or topological disruption upon STR expansion. Fragile X Syndrome (FXS) patients exhibit severe boundary disruption in a manner that correlates with local loss of CTCF occupancy and the degree of FMR1 silencing. Our data uncover higher-order chromatin architecture as a new dimension in understanding repeat expansion disorders.
Overall design Chromosome-Conformation-Capture-Carbon-Copy (5C) was used to interrogate the three-dimensional structure of the genome at the FMR1 locus in 2 normal and 3 FXS B-lymphocyte samples, 1 normal and 1 FXS fibroblast samples, and 2 normal and 2 FXS postmortem cerebellum tissue samples. CTCF ChIP-seq was used to map the binding profile of CTCF genome-wide in 1 normal and 2 FXS B-lymphocyte samples. Two biological replicates of each sample are included.
Contributor(s) Sun J, Zhou L, Phillips-Cremins JE
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Submission date Feb 27, 2018
Last update date Mar 26, 2019
Contact name Jennifer E Phillips-Cremins
Organization name University of Pennsylvania
Department Bioengineering
Street address 210 South 33rd Street
City Philadelphia
State/province Pennsylvania
ZIP/Postal code 19104
Country USA
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (23)
GSM3211725 GM09236_5C_Rep1
GSM3211726 GM09237_5C_Rep1
GSM3211727 GM06890_5C_Rep1
BioProject PRJNA436095
SRA SRP133558

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE111170_4000_pixelmap.bed.gz 11.4 Kb (ftp)(http) BED
GSE111170_GM04025_merged_IP_downsampled_1e-8_pval_thresh_peaks.narrowPeak.gz 1.3 Mb (ftp)(http) NARROWPEAK
GSE111170_GM09236_merged_IP_downsampled_1e-8_pval_thresh_peaks.narrowPeak.gz 1.4 Mb (ftp)(http) NARROWPEAK
GSE111170_GM09237_merged_IP_downsampled_1e-8_pval_thresh_peaks.narrowPeak.gz 1.5 Mb (ftp)(http) NARROWPEAK
GSE111170_RAW.tar 398.2 Mb (http)(custom) TAR (of NARROWPEAK, TXT)
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Raw data are available in SRA
Processed data provided as supplementary file
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