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Series GSE95062 Query DataSets for GSE95062
Status Public on Jul 04, 2017
Title A multipartite enhancer ensemble coordinates pleiotropic developmental functions of Indian hedgehog
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Copy number variations (CNVs) including enhancers frequently appear associated with disease, induced by pathomechanisms that are poorly understood. Here we show through transgenic reporter and genome editing studies in mice that Indian hedgehog (Ihh) is regulated by a constellation of enhancers of unusual complexity and we uncover how duplications within this enhancer architecture cause phenotypes reminiscent of those observed in human patients. At least nine enhancers with distinct combinations of activities orchestrate the expression of Ihh in the digit anlagen, growth plates, skull sutures, and digit tips. Consecutive deletions show that they function in an additive manner resulting in growth defects. Duplications, in contrast, cause not only dose-dependent upregulation of Ihh, but also misexpression, leading to phenotypes influenced by the copy number and relative positioning of individual elements. Taken together, our results uncover a complex regulatory landscape at the Ihh locus and exemplify the intricate and precise control of gene expression during morphogenetic processes.
Overall design Circular Chromosome Conformation Capture (4C-seq) at the Ihh locus in mouse forelimb tissues (digit 2-5) of mutants and WT animals at E14.5.
Contributor(s) Will AJ, Heinrich V, Lupiáñez DG, Mundlos S
Citation(s) 28846100
Submission date Feb 18, 2017
Last update date May 15, 2019
Contact name Darío G Lupiáñez
Organization name Max Planck Institute for Molecular Genetics
Street address Ihnestrasse 73
City Berlin
ZIP/Postal code 14195
Country Germany
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (6)
GSM2495554 4C_WT_IhhTSS_rep1
GSM2495555 4C_WT_IhhTSS_rep2
GSM2495556 4C_Dup-int_IhhTSS_rep1
BioProject PRJNA375879
SRA SRP100285

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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
GSE95062_4C_Ratio_Dup-int_vs_WT.bedgraph.gz 18.8 Kb (ftp)(http) BEDGRAPH
GSE95062_4C_Ratio_Dup-syn_vs_WT.bedgraph.gz 19.8 Kb (ftp)(http) BEDGRAPH
GSE95062_RAW.tar 110.0 Kb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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