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| Status |
Public on Apr 24, 2022 |
| Title |
single cell ATAC-seq |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The chromatin remodeller ATRX interacts with the histone chaperone DAXX, to deposit the histone variant H3.3 at sites of nucleosome turnover. ATRX is known to bind repetitive, heterochromatic regions of the genome including telomeres, ribosomal DNA and pericentric repeats many of which are putative G-quadruplex forming sequences (PQS). At these sites ATRX plays an ancillary role in a wide range of nuclear processes facilitating replication, chromatin modification and transcription. Here, using an improved protocol for chromatin immunoprecipitation, we show that ATRX also binds active regulatory elements in euchromatin. Mutations in ATRX lead to perturbation of gene expression associated with a reduction in chromatin accessibility, histone modification, transcription factor binding and deposition of H3.3 at the sequences to which it normally binds. In erythroid cells where down regulation of a-globin expression is a hallmark of ATR-X syndrome, perturbation of chromatin accessibility and gene expression occurs in only a subset of cells. The stochastic nature of this process suggests that ATRX acts as a general facilitator of cell specific transcriptional and epigenetic programmes, both in heterochromatin and euchromatin.
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| Overall design |
Individuals with exactly the same mutation in the ATRX gene can have variable degrees of a-thalassaemia. This suggests that a-globin gene expression may not be affected in the majority of erythroid cells in ATR-X syndrome and that the presence of a-thalassaemia may be variable even with the same underlying mutation. To determine if there might be cellular heterogeneity associated with changes in chromatin accessibility we performed single-cell ATAC-seq (scATAC-seq) on day10 of CD34+ Hematopoietic Stem Cells differentiation derived from two ATR-X cases with a-thalassaemia and two unaffected donors.
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| Contributor(s) |
Truch J, Scott C |
| Citation(s) |
35710802 |
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| Submission date |
Jan 04, 2022 |
| Last update date |
Jun 27, 2022 |
| Contact name |
Julia Truch |
| Organization name |
University of Oxford
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| Department |
RDM - WIMM
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| Lab |
GIBBONS/HIGGS
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| Street address |
John Radcliffe Hospital, Headley Way, Headington
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| City |
Oxford |
| ZIP/Postal code |
Oxford OX3 9DS |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
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| Relations |
| BioProject |
PRJNA794166 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE193035_RAW.tar |
3.4 Gb |
(http)(custom) |
TAR (of BED, CSV, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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