GSE211074
CHD2 Regulates Neuron-glioma Interactions in Pediatric Glioma
High-grade gliomas (HGG) are deadly diseases for both adult and pediatric patients. Recently, it has been shown that neuronal activity promotes the progression of multiple subgroups of HGG. However, epigenetic mechanisms that govern this process remain elusive. Here we report that the chromatin remodeler CHD2 regulates neuron-glioma interactions in diffuse midline glioma (DMG) characterized by onco-histone H3.1K27M. Depletion of CHD2 in H3.1K27M DMG cells compromises cell viability and neuron-to-glioma synaptic connections in vitro, neuron-induced proliferation of H3.1K27M HGG DMG cells in vitro and in vivo, activity-dependent calcium transients in vivo, and extends the survival of H3.1K27M DMG-bearing mice. Mechanistically, CHD2 coordinates with the transcription factor FOSL1 to control the expression of axon-guidance and synaptic genes in H3.1K27M DMG cells. Together, our study reveals a mechanism whereby CHD2 controls the intrinsic gene program of the H3.1K27M DMG subtype, which in turn regulates the tumor growth-promoting interactions of glioma cells with neurons. Overall design: The CUT&RUN experiments were conducted in WT, CHD2 KO, FOSL1 KO SU-DIPG-IV cells. The markers performed by CUT&RUN methods in DIPG cells included CHD2, FOSL1, H3K4me3, H3K27Ac and H3K27me3.  For the regulation of gene expression, we performed total RNA-seq experiments in WT, CHD2 KO SU-DIPG-IV/SU-DIPG-XVII/SU-DIPG-XXXVI, FOSL1 KO SU-DIPG-IV cells.