{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Siddaway R"],"funding":["Natural Sciences and Engineering Research Council of Canada","ChadTough Foundation","Meagan’s Walk","Garron Family Cancer Centre","DIPG Collaborative","Canadian Institutes of Health Research","Canadian Cancer Society Research Institute","CIHR"],"pagination":["1027-1048"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9547787"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["144(5)"],"pubmed_abstract":["Histone H3 mutations at amino acids 27 (H3K27M) and 34 (H3G34R) are recurrent drivers of pediatric-type high-grade glioma (pHGG). H3K27M mutations lead to global disruption of H3K27me3 through dominant negative PRC2 inhibition, while H3G34R mutations lead to local losses of H3K36me3 through inhibition of SETD2. However, their broader oncogenic mechanisms remain unclear. We characterized the H3.1K27M, H3.3K27M and H3.3G34R interactomes, finding that H3K27M is associated with epigenetic and transcription factor changes; in contrast H3G34R removes a break on cryptic transcription, limits DNA methyltransferase access, and alters mitochondrial metabolism. All 3 mutants had altered interactions with DNA repair proteins and H3K9 methyltransferases. H3K9me3 was reduced in H3K27M-containing nucleos"],"journal":["Acta neuropathologica"],"pubmed_title":["Oncohistone interactome profiling uncovers contrasting oncogenic mechanisms and identifies potential therapeutic targets in high grade glioma."],"pmcid":["PMC9547787"],"funding_grant_id":["702296","PJT-156407","PJT-159683","706160","RGPIN-2016-05559"],"pubmed_authors":["Vadivel Anguraj AK","Coyaud E","Portante A","Hawkins C","Canty L","Campos EI","Pajovic S","Lubanszky E","Raught B","Siddaway R","Carette S","Milos S","Zhang C","Moran MF","Yun HY","Sbergio SG"],"additional_accession":[]},"is_claimable":false,"name":"Oncohistone interactome profiling uncovers contrasting oncogenic mechanisms and identifies potential therapeutic targets in high grade glioma.","description":"Histone H3 mutations at amino acids 27 (H3K27M) and 34 (H3G34R) are recurrent drivers of pediatric-type high-grade glioma (pHGG). H3K27M mutations lead to global disruption of H3K27me3 through dominant negative PRC2 inhibition, while H3G34R mutations lead to local losses of H3K36me3 through inhibition of SETD2. However, their broader oncogenic mechanisms remain unclear. We characterized the H3.1K27M, H3.3K27M and H3.3G34R interactomes, finding that H3K27M is associated with epigenetic and transcription factor changes; in contrast H3G34R removes a break on cryptic transcription, limits DNA methyltransferase access, and alters mitochondrial metabolism. All 3 mutants had altered interactions with DNA repair proteins and H3K9 methyltransferases. H3K9me3 was reduced in H3K27M-containing nucleos","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2026-06-01T02:11:01.771Z","creation":"2025-02-19T01:28:36.143Z"},"accession":"S-EPMC9547787","cross_references":{"pubmed":["36070144"],"doi":["10.1007/s00401-022-02489-2"]}}