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Series GSE212919 Query DataSets for GSE212919
Status Public on Sep 27, 2023
Title Characterization of open chromatin regions and ATRX, DAXX, H3.3 and cGAS binding sites in BJ-hTERT cells mutant for ATRX, on cGAS WT or null background
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Mutations in the chromatin remodeller X-linked α-thalassaemia intellectual disability syndrome protein (ATRX) are a well-recognised cause of developmental problems in males. In two patients demonstrating white matter disease, intracranial calcification and learning difficulties, we identified a persistent upregulation of interferon stimulated gene expression, and the same Y1758C mutation in ATRX. We describe this substitution, and other ‘classical’ ATRX syndrome-associated loss-of-function mutations, to result in enhanced interferon signalling, and that while this effect is dependent on cGAS it is not mediated by cGAMP. Taking advantage of the retained expression of Y1758C mutant protein, we demonstrate a redistribution of mutant-ATRX/DAXX/H3.3 complex and cGAS at open chromatin in cGAS wild-type, but not in cGAS-null, cells. Thus, we show that ATRX is essential for the homeostatic control of type I interferon signalling, and that cGAS mediates differential genomic binding of mutant ATRX, and a preferential association with DAXX and H3.3 at accessible chromatin, leading to changes in gene expression.
Overall design Cleavage under targets & tagmentation (CUT&Tag) using anti-ATRX, anti-DAXX, anti-H3.3 and anti-cGAS antibodies; and cleavage under targeted accessible chromatin (CUTAC) using anti-H3K4me2 antibody.
Contributor(s) El-Daher M, Grimes GR, Crow YJ
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Submission date Sep 08, 2022
Last update date Sep 27, 2023
Contact name Graeme Richard Grimes
Organization name University of Edinburgh, The Institute of Genetics and Cancer
Department Human Genetics Unit
Lab Bioinformatics Analysis Core
Street address Western General Hospital, Crewe Road
City Edinburgh
ZIP/Postal code EH4 2XU
Country United Kingdom
Platforms (1)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (44)
GSM6561076 cGAS-WT, ATRX-WT, Rep1, ATRX
GSM6561077 cGAS-WT, ATRX-WT, Rep2, ATRX
GSM6561078 cGAS-WT, ATRX-KI, Rep1, ATRX
This SubSeries is part of SuperSeries:
GSE212923 Mutation of ATRX induces type I interferon signalling and defines a non-canonical role of nuclear cGAS in the regulation of chromatin state
BioProject PRJNA878469

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Supplementary file Size Download File type/resource
GSE212919_RAW.tar 6.2 Mb (http)(custom) TAR (of BED)
GSE212919_cGAS-KO_ATRX-KI_merged_ATRX.bed.gz 338.1 Kb (ftp)(http) BED
GSE212919_cGAS-KO_ATRX-KI_merged_CUTAC.bed.gz 653.8 Kb (ftp)(http) BED
GSE212919_cGAS-KO_ATRX-KI_merged_DAXX.bed.gz 339.8 Kb (ftp)(http) BED
GSE212919_cGAS-KO_ATRX-KI_merged_H3.3.bed.gz 546.5 Kb (ftp)(http) BED
GSE212919_cGAS-KO_ATRX-KO_merged_CUTAC.bed.gz 630.0 Kb (ftp)(http) BED
GSE212919_cGAS-KO_ATRX-WT_merged_ATRX.bed.gz 250.5 Kb (ftp)(http) BED
GSE212919_cGAS-KO_ATRX-WT_merged_CUTAC.bed.gz 692.9 Kb (ftp)(http) BED
GSE212919_cGAS-KO_ATRX-WT_merged_DAXX.bed.gz 340.6 Kb (ftp)(http) BED
GSE212919_cGAS-KO_ATRX-WT_merged_H3.3.bed.gz 564.5 Kb (ftp)(http) BED
GSE212919_cGAS-KO_ATRX-WT_merged_cGAS.bed.gz 443.3 Kb (ftp)(http) BED
GSE212919_cGAS-WT_ATRX-KI_merged_ATRX.bed.gz 252.8 Kb (ftp)(http) BED
GSE212919_cGAS-WT_ATRX-KI_merged_CUTAC.bed.gz 252.9 Kb (ftp)(http) BED
GSE212919_cGAS-WT_ATRX-KI_merged_DAXX.bed.gz 234.3 Kb (ftp)(http) BED
GSE212919_cGAS-WT_ATRX-KI_merged_H3.3.bed.gz 435.8 Kb (ftp)(http) BED
GSE212919_cGAS-WT_ATRX-KI_merged_cGAS.bed.gz 457.1 Kb (ftp)(http) BED
GSE212919_cGAS-WT_ATRX-KO_merged_CUTAC.bed.gz 635.2 Kb (ftp)(http) BED
GSE212919_cGAS-WT_ATRX-WT_merged_ATRX.bed.gz 634.1 Kb (ftp)(http) BED
GSE212919_cGAS-WT_ATRX-WT_merged_CUTAC.bed.gz 556.6 Kb (ftp)(http) BED
GSE212919_cGAS-WT_ATRX-WT_merged_DAXX.bed.gz 230.3 Kb (ftp)(http) BED
GSE212919_cGAS-WT_ATRX-WT_merged_H3.3.bed.gz 761.4 Kb (ftp)(http) BED
GSE212919_cGAS-WT_ATRX-WT_merged_cGAS.bed.gz 452.2 Kb (ftp)(http) BED
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Processed data provided as supplementary file
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