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Series GSE148185 Query DataSets for GSE148185
Status Public on Apr 07, 2020
Title Three-dimensional chromatin interactions remain stable upon CAG/CTG repeat expansion
Organism Homo sapiens
Experiment type Other
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Summary Expanded CAG/CTG repeats underlie thirteen neurological disorders, including myotonic dystrophy type 1 (DM1) and Huntington’s disease (HD). Upon expansion, CAG/CTG repeat loci acquire heterochromatic characteristics. This observation raises the hypothesis that repeat expansion provokes changes to higher-order chromatin conformation and thereby affects both gene expression in cis and the genetic instability of the repeat tract. Here we tested this hypothesis directly by performing 4C sequencing at the DMPK and HTT loci from DM1 and HD patient-derived cells. Surprisingly, chromatin contacts remain unchanged upon repeat expansion at both loci. This was true for expanded alleles with different DNA methylation levels and CTCF binding. Repeat tract sizes ranging from 15 to 1,700 repeats displayed strikingly similar chromatin interaction profiles. Moreover, the ectopic insertion of an expanded CAG repeat tract did not change the three-dimensional chromatin conformation of the surrounding genomic region. Our findings argue that extensive changes in heterochromatic properties are not enough to alter chromatin conformation at expanded CAG/CTG repeat loci. We conclude that 3D chromatin conformation is unlikely to drive repeat expansions or changes in gene expression in expanded CAG/CTG repeat disorders.

This SuperSeries is composed of the SubSeries listed below.
Overall design Refer to individual Series
Citation(s) 32656337
Submission date Apr 06, 2020
Last update date Jul 17, 2020
Contact name Gustavo Agustín Ruiz Buendía
Organization name University of Lausanne
Department Center for Integrative Genomics
Street address University of Lausanne
City Lausanne
State/province Vaud
ZIP/Postal code 1015
Country Switzerland
Platforms (3)
GPL15520 Illumina MiSeq (Homo sapiens)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (275)
GSM4455561 4C_ACTA1_GM02164_rep1
GSM4455562 4C_ACTA1_GM02164_rep2
GSM4455563 4C_ACTA1_GM02164_rep3
This SuperSeries is composed of the following SubSeries:
GSE148176 4C-seq: Three-dimensional chromatin interactions of FMR1, HTT, DMPK, and GFP viewpoints.
GSE148177 Bisulfite-seq: Analysis of CpG methylation at two CTCF binding sites flanking the CTG repeats of DMPK.
GSE148179 ChIP-seq: Analysis of CTCF occupancy in unaffected and DM1 patient lymphoblastoid cell lines.
BioProject PRJNA623390

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
GSE148185_RAW.tar 1.9 Gb (http)(custom) TAR (of BEDGRAPH, BIGWIG, TXT, VCF)
SRA Run SelectorHelp

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