Radiotherapy Reshapes the 3D Genome in Medulloblastoma Cells
Radiotherapy is central to medulloblastoma treatment, yet the molecular and three-dimensional (3D) genome responses to irradiation remain poorly understood. Here, we integrated RNA sequencing, proteomics, and Micro-C to characterise the response of ONS-76 medulloblastoma cells to clinically relevant radiation exposures. A single 2 Gy dose induced widespread transcriptional and proteomic changes,…
Radiotherapy plays a crucial role in treating medulloblastoma, but the molecular and three-dimensional genome responses to radiation are not well understood. To address this, researchers integrated RNA sequencing, proteomics, and Micro-C to analyze the effects of clinically relevant radiation on ONS-76 medulloblastoma cells.
A single 2 Gy dose of radiation led to extensive changes in transcription and protein production, impacting cell adhesion, migration, DNA replication, and ribosome biogenesis pathways. Further analysis identified LAMB3 and AKR1B10 as potential mediators of the cells' response to radiation, with these proteins remaining elevated even after fractionated doses.
Micro-C profiling revealed that radiation caused significant changes in the three-dimensional organization of the genome. While the overall genome structure remained relatively stable, irradiation promoted an increased presence of active A compartments and the formation of new topologically associated domains (TADs) boundaries. Additionally, radiation led to transient strengthening of TAD boundaries.
These findings offer the first comprehensive characterization of radiation-induced changes in the three-dimensional chromatin structure in a medulloblastoma model. The study also highlights specific molecular and structural features that may be associated with the cells' response to radiation therapy.
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