|
| Status |
Public on Jul 19, 2022 |
| Title |
DAXX-ATRX-H3.3 Regulation of p53 Chromatin Binding and DNA Damage Response [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
DAXX and ATRX are tumor suppressor proteins that form a complex with histone H3.3 chaperone and are frequently mutated in cancers with the alternative lengthening of telomeres (ALT), such as pediatric glioblastoma. Rapid loss of function of either DAXX or ATRX are not by themselves sufficient to induce the ALT phenotype. However, cells lacking DAXX or ATRX can be readily selected for ALT-like features. Here, we show that a key feature of ALT selected DAXX and ATRX null glioblastoma cells is the attenuation of p53 function. RNA-seq analysis of DAXX or ATRX null U87 glioblastoma cells with ALT-like features revealed that p53 pathway is among perturbed. ALT-selected DAXX and ATRX-null cells had aberrant response to DNA damaging agent etoposide. Both DAXX and ATRX-null ALT cells showed a loss of p53 binding at a subset of response elements. Complementation of DAXX null cells with wt DAXX rescued p53 binding and transcription, while the tumor associated mutation L130R, that disrupts ATRX binding, was incapable of rescuing p53 chromatin binding. We show that histone H3.3 binding is reduced in DAXX-null cells especially at subtelomeric p53 binding sites and telomere repeats. These findings indicate that DAXX and ATRX function to enable p53 chromatin binding through modulation of histone H3.3 binding, especially at sub-telomeric sites.
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| |
|
| Overall design |
CHIP-seq of p53 in DAXX WT and KO conditions in etoposide treated cells
|
| Web link |
https://pubmed.ncbi.nlm.nih.gov/36028493/
|
| |
|
| Contributor(s) |
Lieberman P, Gulve N |
| Citation(s) |
36028493 |
| |
| Submission date |
Oct 22, 2021 |
| Last update date |
Oct 18, 2022 |
| Contact name |
Priyankara J Wickramasinghe |
| E-mail(s) |
[email protected]
|
| Phone |
2154956837
|
| Organization name |
The Wistar Institute
|
| Department |
Bioinformatics
|
| Lab |
Genomics
|
| Street address |
3601 Spruce Street
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (6)
|
|
| This SubSeries is part of SuperSeries: |
| GSE186443 |
DAXX-ATRX-H3.3 Regulation of p53 Chromatin Binding and DNA Damage Response |
|
| Relations |
| BioProject |
PRJNA773795 |
| SRA |
SRP342749 |
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