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| 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
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| 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.
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| 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.
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| Contributor(s) |
El-Daher M, Grimes GR, Crow YJ |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Sep 08, 2022 |
| Last update date |
Sep 27, 2023 |
| Contact name |
Graeme Richard Grimes |
| E-mail(s) |
graeme.grimes@ed.ac.uk
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| Organization name |
University of Edinburgh, The Institute of Genetics and Cancer
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| Department |
Human Genetics Unit
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| Lab |
Bioinformatics Analysis Core
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| Street address |
Western General Hospital, Crewe Road
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| City |
Edinburgh |
| ZIP/Postal code |
EH4 2XU |
| Country |
United Kingdom |
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| Platforms (1) |
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| Samples (44)
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| GSM6561079 |
cGAS-WT, ATRX-KI, Rep2, ATRX |
| GSM6561080 |
cGAS-KO, ATRX-WT, Rep1, ATRX |
| GSM6561081 |
cGAS-KO, ATRX-WT, Rep2, ATRX |
| GSM6561082 |
cGAS-KO, ATRX-KI, Rep1, ATRX |
| GSM6561083 |
cGAS-KO, ATRX-KI, Rep2, ATRX |
| GSM6561084 |
cGAS-WT, ATRX-WT, Rep1, DAXX |
| GSM6561085 |
cGAS-WT, ATRX-WT, Rep2, DAXX |
| GSM6561086 |
cGAS-WT, ATRX-KI, Rep1, DAXX |
| GSM6561087 |
cGAS-WT, ATRX-KI, Rep2, DAXX |
| GSM6561088 |
cGAS-KO, ATRX-WT, Rep1, DAXX |
| GSM6561089 |
cGAS-KO, ATRX-WT, Rep2, DAXX |
| GSM6561090 |
cGAS-KO, ATRX-KI, Rep1, DAXX |
| GSM6561091 |
cGAS-KO, ATRX-KI, Rep2, DAXX |
| GSM6561092 |
cGAS-WT, ATRX-WT, Rep1, H3.3 |
| GSM6561093 |
cGAS-WT, ATRX-WT, Rep2, H3.3 |
| GSM6561094 |
cGAS-WT, ATRX-KI, Rep1, H3.3 |
| GSM6561095 |
cGAS-WT, ATRX-KI, Rep2, H3.3 |
| GSM6561096 |
cGAS-KO, ATRX-WT, Rep1, H3.3 |
| GSM6561097 |
cGAS-KO, ATRX-WT, Rep2, H3.3 |
| GSM6561098 |
cGAS-KO, ATRX-KI, Rep1, H3.3 |
| GSM6561099 |
cGAS-KO, ATRX-KI, Rep2, H3.3 |
| GSM6561100 |
cGAS-WT, ATRX-WT, Rep1, CUTAC |
| GSM6561101 |
cGAS-WT, ATRX-WT, Rep2, CUTAC |
| GSM6561102 |
cGAS-WT, ATRX-KI, Rep1, CUTAC |
| GSM6561103 |
cGAS-WT, ATRX-KI, Rep2, CUTAC |
| GSM6561104 |
cGAS-WT, ATRX-KO, Rep1, CUTAC |
| GSM6561105 |
cGAS-WT, ATRX-KO, Rep2, CUTAC |
| GSM6561106 |
cGAS-KO, ATRX-WT, Rep1, CUTAC |
| GSM6561107 |
cGAS-KO, ATRX-WT, Rep2, CUTAC |
| GSM6561108 |
cGAS-KO, ATRX-KI, Rep1, CUTAC |
| GSM6561109 |
cGAS-KO, ATRX-KI, Rep2, CUTAC |
| GSM6561110 |
cGAS-KO, ATRX-KO, Rep1, CUTAC |
| GSM6561111 |
cGAS-KO, ATRX-KO, Rep2, CUTAC |
| GSM6561112 |
cGAS-WT, ATRX-WT, Rep1, cGAS |
| GSM6561113 |
cGAS-WT, ATRX-WT, Rep2, cGAS |
| GSM6561114 |
cGAS-WT, ATRX-KI, Rep1, cGAS |
| GSM6561115 |
cGAS-WT, ATRX-KI, Rep2, cGAS |
| GSM6561116 |
cGAS-KO, ATRX-WT, Rep1, cGAS |
| GSM6561117 |
cGAS-KO, ATRX-WT, Rep2, cGAS |
| GSM6561118 |
cGAS-WT, ATRX-WT, Rep1, IgG |
| GSM6561119 |
cGAS-KO, ATRX-WT, Rep1, IgG |
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| 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 |
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| Relations |
| BioProject |
PRJNA878469 |
| 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 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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