GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE348nnn/GSE348366/primary200OKGenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE348366GEOGSEfalseSuper-enhancer-driven MAFK promotes glioblastoma growth by transcriptionally activating immune-related genes and is stabilized by the deubiquitinase USP36Glioblastoma (GBM) is the most aggressive primary malignant tumor of the adult central nervous system, with a median survival of less than 15 months despite surgery combined with radiochemotherapy. Super-enhancers (SEs) are large clusters of cis-regulatory elements densely marked by H3K27ac that drive high-level expression of key oncogenes. In this study, we systematically identified SE-regulated genes in GBM by integrating H3K27ac ChIP-seq data from five glioma cell lines and applying the ROSE algorithm. We report for the first time that MAFK, a small Maf family transcription factor, is controlled by an SE in GBM. Three-dimensional genome profiling revealed prominent long-range chromatin interactions between the MAFK-SE and the MAFK locus, and E2 was delineated as the principal active enhancer element. Functionally, MAFK depletion markedly impaired GBM cell proliferation, induced G2/M arrest and apoptosis in vitro, and suppressed subcutaneous xenograft growth in vivo. Integrative RNA-seq and CUT&Tag analyses showed that MAFK directly binds and transcriptionally activates immune-related genes, including IL6, IRF1, STAT1, NFKB1 and JAK2, implicating it in the regulation of GBM cell immune responses. Moreover, co-immunoprecipitation coupled with mass spectrometry identified the deubiquitinase USP36 as a novel MAFK-interacting protein. USP36 selectively removed K48-linked polyubiquitin chains from MAFK, thereby protecting it from proteasomal degradation and sustaining its steady-state level. Collectively, these data uncover a SE–MAFK–USP36 regulatory axis that drives GBM progression and nominate MAFK as a potential therapeutic target.2026/09/28GSE348366GSM10071077GSM1007107624676348366Homo sapiens