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Series GSE123388 Query DataSets for GSE123388
Status Public on May 13, 2019
Title A Preformed Chromatin Architecture Ensures Robust Shh Transcription during Limb Development
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
Summary During embryogenesis, enhancer-promoter interactions control gene transcriptional activation. These interactions can be tissue-specific or tissue-invariant and occur mostly within larger insulated regulatory domains called Topologically Associating Domains (TADs). Boundary elements, which delineate the extent of TADs, frequently interact with each other and have been associated with constitutive transcription and CTCF/Cohesin binding. In this work, we set out to investigate the regulatory role of a tissue-invariant, preformed interaction between two boundaries that involve the Shh gene and its unique limb enhancer, the ZRS, located one megabase away. Using CRISPR/Cas9 we specifically perturb CTCF binding sites or constitutive transcription at the ZRS-containing boundary, without altering the enhancer sequence. Using capture-HiC (cHiC) we show that both types of perturbation result in altered preformed chromatin interactions and lead to a reduction of Shh expression in developing limb buds. Finally, we demonstrate that the disruption of the chromatin structure in combination with a hypomorphic ZRS allele results in a dramatic Shh loss- of- function and digit agenesis. We thus propose that preformed chromatin structures can ensure stable enhancer promoter communication during development and robustness of gene transcriptional activation.

This SuperSeries is composed of the SubSeries listed below.
 
Overall design Refer to individual Series
 
Citation(s) 31147463
Submission date Dec 06, 2018
Last update date Jan 26, 2023
Contact name Christina Paliou
E-mail(s) paliou@molgen.mpg.de
Organization name Max Planck Institute for Molecular Genetics
Street address Ihnestrasse 63-73
City Berlin
ZIP/Postal code 14195
Country Germany
 
Platforms (3)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (54)
GSM3502439 746_WT_Shh_TSS_Rep1
GSM3502440 747_WT_Shh_TSS_Rep2
GSM3502441 748_Lmbr1Dprom_Shh TSS_Rep1
This SuperSeries is composed of the following SubSeries:
GSE123382 A Preformed Chromatin Architecture Ensures Robust Shh Transcription during Limb Development [4C-seq]
GSE123383 A Preformed Chromatin Architecture Ensures Robust Shh Transcription during Limb Development [ATAC-seq]
GSE123384 A Preformed Chromatin Architecture Ensures Robust Shh Transcription during Limb Development [Capture Hi-C]
Relations
BioProject PRJNA508608

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
GSE123388_RAW.tar 8.2 Gb (http)(custom) TAR (of BEDGRAPH, BW)
SRA Run SelectorHelp

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