{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sardar D"],"funding":["NIDCD NIH HHS","NINDS NIH HHS","NCI NIH HHS","NIH HHS"],"pagination":["e2202015119"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9303974"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["119(29)"],"pubmed_abstract":["Epigenetic dysregulation is a universal feature of cancer that results in altered patterns of gene expression that drive malignancy. Brain tumors exhibit subtype-specific epigenetic alterations; however, the molecular mechanisms responsible for these diverse epigenetic states remain unclear. Here, we show that the developmental transcription factor Sox9 differentially regulates epigenomic states in high-grade glioma (HGG) and ependymoma (EPN). Using our autochthonous mouse models, we found that Sox9 suppresses HGG growth and expands associated H3K27ac states, while promoting ZFTA-RELA (ZR<sup>FUS</sup>) EPN growth and diminishing H3K27ac states. These contrasting roles for Sox9 correspond with protein interactions with histone deacetylating complexes in HGG and an association with the ZR<sup>FUS</sup> oncofusion in EPN. Mechanistic studies revealed extensive Sox9 and ZR<sup>FUS</sup> promoter co-occupancy, indicating functional synergy in promoting EPN tumorigenesis. Together, our studies demonstrate how epigenomic states are differentially regulated in distinct subtypes of brain tumors, while revealing divergent roles for Sox9 in HGG and EPN tumorigenesis."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Sox9 directs divergent epigenomic states in brain tumor subtypes."],"pmcid":["PMC9303974"],"funding_grant_id":["K99 DC019668","S10 OD026804","R01 NS124093","U01 CA217842","R01 NS071153","R01 NS094615","P30 CA125123"],"pubmed_authors":["Sardar D","Rajendran K","Jalali A","Reyes A","Cervantes A","Yu K","Varadharajan S","Jain A","Chen HC","Rao G","Deneen B","Mohila C","Lozzi B","Curry R","Mack SC"],"additional_accession":[]},"is_claimable":false,"name":"Sox9 directs divergent epigenomic states in brain tumor subtypes.","description":"Epigenetic dysregulation is a universal feature of cancer that results in altered patterns of gene expression that drive malignancy. Brain tumors exhibit subtype-specific epigenetic alterations; however, the molecular mechanisms responsible for these diverse epigenetic states remain unclear. Here, we show that the developmental transcription factor Sox9 differentially regulates epigenomic states in high-grade glioma (HGG) and ependymoma (EPN). Using our autochthonous mouse models, we found that Sox9 suppresses HGG growth and expands associated H3K27ac states, while promoting ZFTA-RELA (ZR<sup>FUS</sup>) EPN growth and diminishing H3K27ac states. These contrasting roles for Sox9 correspond with protein interactions with histone deacetylating complexes in HGG and an association with the ZR<sup>FUS</sup> oncofusion in EPN. Mechanistic studies revealed extensive Sox9 and ZR<sup>FUS</sup> promoter co-occupancy, indicating functional synergy in promoting EPN tumorigenesis. Together, our studies demonstrate how epigenomic states are differentially regulated in distinct subtypes of brain tumors, while revealing divergent roles for Sox9 in HGG and EPN tumorigenesis.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2025-04-04T20:32:45.764Z","creation":"2025-04-04T20:32:45.764Z"},"accession":"S-EPMC9303974","cross_references":{"pubmed":["35858326"],"doi":["10.1073/pnas.2202015119"]}}