GEO series

Disruptions of Topological Chromatin Domains Causes Pathogenic Rewiring of Gene-Enhancer Interactions [4C-Seq-human]

GSE66378 Homo sapiens (human) Other 6 samples Submitted 2015/05/08 Platform GPL15433Platform GPL11154

At a glance

human · 6 samples

Organism: Homo sapiens (human)
Samples: 6 samples
Data you can get: A processed table (series matrix) and supplementary files from NCBI.

Summary (written by the submitters)

Mammalian genomes are organized into megabase-scale topologically associated domains (TADs) that have been proposed to represent large regulatory units. Here we demonstrate that disruption of TADs can cause rewiring of long-range regulatory architecture and result in pathogenic phenotypes. We show that distinct human limb malformations are caused by deletions, inversions, or duplications altering the structure of the TAD-spanning WNT6/IHH/EPHA4/PAX3 locus.

Read the full summary ↓

Using CRISPR/Cas genome editing, we generated mice with corresponding rearrangements. Both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding DNA, and a cluster of limb enhancers normally associated with Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression of another gene in the locus. Our results demonstrate the functional importance of TADs for orchestrating gene expression via genome architecture and indicate criteria for predicting the pathogenicity of human structural variants, particularly in non-coding regions of the human genome.

This dataset

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Direct links to NCBI, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need.

All supplementary files ↗

3 · The original raw files

Whole study · RAW.tar

Everything the authors deposited as one archive (GSE66378_RAW.tar), including the raw array or instrument files. Can be large; the picker in step 2 takes just the samples you need.

Whole study · RAW.tar ↓

Also filed as BioProject PRJNA276692 and SRA study SRP055672. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 25959774) ↗

Samples in this study

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