ATRX inactivation disrupts global chromatin state and topology to dysregulate neurodevelopmental pathways in glioma pathogenesis - PubMed
3 hours ago
- #glioma
- #ATRX
- #chromatin topology
- ATRX inactivation disrupts global chromatin state and topology, leading to dysregulation of neurodevelopmental pathways in glioma pathogenesis.
- Loss of Atrx in murine neuroepithelial progenitors impacts 3D chromatin architecture, altering topologically associating domains (TADs) and CTCF binding sites at neurodevelopmental genes.
- Changes include disruptions in H3K9me3-marked laminin-associated domains and reprogramming of enhancer/superenhancer regions at genes like Slitrk6 and the HoxA cluster.
- Pharmacologic inhibition of HOXA-PBX binding selectively impairs in vivo growth of patient-derived ATRX-deficient glioma stem cells, suggesting a therapeutic target.