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Series GSE186440 Query DataSets for GSE186440
Status Public on Jul 19, 2022
Title DAXX-ATRX-H3.3 Regulation of p53 Chromatin Binding and DNA Damage Response [RNA-Seq]
Organism Homo sapiens
Experiment type Expression 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.
 
Overall design RNA-seq of DAXX and ATRX WT and KO conditions in control and 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) priyaw@wistar.org
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 (24)
GSM5651625 DAXX WT cells, untreated, replicate 1
GSM5651626 DAXX WT cells, untreated, replicate 2
GSM5651627 DAXX WT cells, untreated, replicate 3
This SubSeries is part of SuperSeries:
GSE186443 DAXX-ATRX-H3.3 Regulation of p53 Chromatin Binding and DNA Damage Response
Relations
BioProject PRJNA773796
SRA SRP342748

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE186440_DAXX_ATRX_RNAseq.txt.gz 934.8 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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