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| Status |
Public on Apr 15, 2024 |
| Title |
Rapid PTEFb-dependent transcriptional reorganization underpins the glioma adaptive response to radiotherapy [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Using a combination of ChIP-, ATAC-, RNA-seq, and CUT&RUN in model systems of diffuse intrinsic pontine glioma and other pediatric high-grade gliomas, we observe a rapid genome-wide reorganization of active chromatin within hours of exposure to therapeutic ionizing radiation. This redistribution facilitates PTEFb-mediated pause-release of Pol II to drive nascent transcriptional induction of canonical DNA damage response programs. Concurrent inhibition of PTEFb imparts a transcription elongation defect, disrupting this chromatin reorganization and blunting transcriptional induction. Functionally, concurrent PTEFb inhibition abrogates key adaptive programs such as DNA damage repair and cell cycle regulation. This combination demonstrates a potent, synergistic therapeutic potential agnostic of glioma subtype, leading to a marked induction of tumor cell apoptosis and prolongation of xenograft survival.
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| Overall design |
H3K27ac ChIP-seq was conducted in the SU-DIPG4 cell line after 6 Gy radiation in the presence or absence of AZD4573.
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| Contributor(s) |
Martin Sobral L, Walker F, Danis E, Dahl N |
| Citation(s) |
38816355 |
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| Submission date |
Mar 21, 2023 |
| Last update date |
Jun 12, 2024 |
| Contact name |
Etienne Danis |
| E-mail(s) |
ETIENNE.DANIS@CUANSCHUTZ.EDU
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| Organization name |
University of Colorado, Denver - Anschutz Medical Campus
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| Department |
Cancer Center
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| Street address |
13001 E 17th Pl
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| City |
AURORA |
| State/province |
CO |
| ZIP/Postal code |
80045 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| GSM7108307 |
Histone_3_K27_acetylation, DIPG4, DMSO, replicate 1 |
| GSM7108308 |
Histone_3_K27_acetylation, DIPG4, DMSO, replicate 2 |
| GSM7108309 |
Histone_3_K27_acetylation, DIPG4, DMSO, radiation, replicate 1 |
| GSM7108310 |
Histone_3_K27_acetylation, DIPG4, DMSO, radiation, replicate 2 |
| GSM7108311 |
Histone_3_K27_acetylation, DIPG4, AZD4573, radiation, replicate 1 |
| GSM7108312 |
Histone_3_K27_acetylation, DIPG4, AZD4573, radiation, replicate 2 |
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| This SubSeries is part of SuperSeries: |
| GSE227797 |
Rapid PTEFb-dependent transcriptional reorganization underpins the glioma adaptive response to radiotherapy |
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| Relations |
| BioProject |
PRJNA947083 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE227796_RAW.tar |
1.1 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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