Zhang, Xu, Duan, Shoufu, Apostolou, Panagiota E, Wu, Xiaoping, Watanabe, Jun, Gallitto, Matthew, Barron, Tara, Taylor, Kathryn R, Woo, Pamelyn J, Hua, Xu, Zhou, Hui, Wei, Hong-Jian, McQuillan, Nicholas, Kang, Kyung-Don, Friedman, Gregory K, Canoll, Peter D, Chang, Kenneth, Wu, Cheng-Chia, Hashizume, Rintaro, Vakoc, Christopher R, Monje, Michelle, McKhann, Guy M, Gogos, Joseph A, Zhang, Zhiguo (May 2024) CHD2 Regulates Neuron-glioma Interactions in Pediatric Glioma. Cancer Discovery. ISSN 2159-8274
Abstract
High-grade gliomas (HGG) are deadly diseases for both adult and pediatric patients. Recently, it has been shown that neuronal activity promotes 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 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.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics diseases & disorders > cancer diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > histone bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types |
| CSHL Authors: | |
| Communities: | CSHL labs > Chang lab CSHL labs > Vakoc lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 20 May 2024 |
| Date Deposited: | 28 May 2024 13:01 |
| Last Modified: | 20 Nov 2024 16:26 |
| PMCID: | PMC11456263 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/41565 |
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