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| Status |
Public on Nov 19, 2023 |
| Title |
Paediatric Glioma Histone H3.3 K27M/G34R Mutations Drive Abnormalities in Phase-Separated PML Nuclear Bodies. |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Point mutations in histone variant H3.3 (H3.3 K27M, H3.3 G34R) and the H3.3-specific ATRX/DAXX chaperone complex are frequent events in paediatric gliomas. It is clear that H3.3 point mutations affect many chromatin modifications but the exact oncogenic mechanisms are an area of active investigation. Histone H3.3 has been previously linked to PML, a gene which is frequently mutated in Acute Promyelocytic Leukaemia. We find that H3.3 point mutations disrupt the formation of PML nuclear bodies and this prevents differentiation down glial lineages. Similar to PML-mutated Acute Promyelocytic Leukaemias, H3.3-mutated patient-derived gliomas cells are also sensitive to drugs which target PML bodies. We identify PML as a contributor to oncogenesis in H3.3-mutated gliomas and our results indicate that PML-targeting strategies may prove effective at treating H3.3-mutated paediatric gliomas.
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| Overall design |
ChIP sequencing of H3.3 and PML in H3.3 K27M, H3.3 G34R, and ATRX KO/G34R mutated mouse ES cells. ChIP-sequencing of H3.3 in H3.3 K27M and H3.3 K27MKO corrected DIPG XIII and BT245 patient-derived glioma cells.
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| Web link |
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-023-03122-5
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| |
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| Contributor(s) |
Voon HP, Wong LH |
| Citation(s) |
38066546 |
| |
| Submission date |
Aug 01, 2022 |
| Last update date |
Dec 10, 2023 |
| Contact name |
Hsiao Phin Joanna Voon |
| E-mail(s) |
Joanna.Voon@monash.edu
|
| Organization name |
Monash University
|
| Department |
Biochemistry and Molecular Biology
|
| Lab |
Epigenetics and Chromatin
|
| Street address |
Monash University, Wellington Road
|
| City |
Clayton |
| State/province |
Victoria |
| ZIP/Postal code |
3800 |
| Country |
Australia |
| |
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| Platforms (3) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
| GPL21697 |
NextSeq 550 (Homo sapiens) |
|
| Samples (26)
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| Relations |
| BioProject |
PRJNA864751 |
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