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Series GSE130659 Query DataSets for GSE130659
Status Public on Mar 09, 2021
Title Cornelia-de-Lange syndrome associated mutations cause a DNA damage signalling and repair defect
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Cornelia de Lange Syndrome is a multisystem developmental disorder typically caused by mutations in the gene encoding the cohesin loader NIPBL. The associated phenotype is generally assumed to be the consequence of aberrant transcriptional regulation. Recently, we identified a residue substitution in BRD4 associated with a Cornelia de Lange-like Syndrome, that reduces BRD4 binding to acetylated histones. Here we show that, although this mutation reduces BRD4-enhancer interaction in mouse embryonic stem cells, it does not affect transcription. Rather it delays the cell cycle, increased DNA damage signalling, and perturbs regulation of DNA repair in mutant cells. This uncovers a new role for BRD4 in DNA repair pathway choice. Furthermore, we find evidence of a similar increase in DNA damage signalling in cells derived from NIPBL-deficient individuals, suggesting that defective DNA damage signalling and repair is also a feature of typical Cornelia de Lange Syndrome.
Overall design Examination of Y430C BRD4 mutation in mESCs. Two cell lines were used, a wild type one (WT) and CRISPR-Cas9 generated Y430C mutant one (MUT)
Contributor(s) Olley G, Madapura PM, FitzPatrick DR, Bickmore WA, Boumendil C
Citation(s) 34035299
Submission date May 03, 2019
Last update date Jun 09, 2021
Contact name Ilya M. Flyamer
Organization name University of Edinburgh
Department IGMM, HGU
Lab Bickmore
Street address Crewe Road, Western General Hospital
City Edinburgh
ZIP/Postal code EH4 2GH
Country United Kingdom
Platforms (1)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (18)
GSM3746514 spiked in RNAseq WT replicate 1
GSM3746515 spiked in RNAseq WT replicate 2
GSM3746516 spiked in RNAseq WT replicate 3
BioProject PRJNA540927
SRA SRP194726

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Supplementary file Size Download File type/resource
GSE130659_RAW.tar 1.9 Gb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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