Inhibition of the tumour suppressive function of p53 (encoded by TP53) is paramount for cancer development in humans. However, p53 remains unmutated in the majority of cases of glioblastoma (GBM)—the most common and deadly adult brain malignancy1,2. Thus, how p53-mediated tumour suppression is countered in TP53 wild-type (TP53WT) GBM is unknown. Here we describe a GBM-specific epigenetic mechanism in which the chromatin regulator bromodomain-containing protein 8 (BRD8) maintains H2AZ occupancy at p53 target loci through the EP400 histone acetyltransferase complex. This mechanism causes a repressive chromatin state that prevents transactivation by p53 and sustains proliferation. Notably, targeting the bromodomain of BRD8 displaces H2AZ, enhances chromatin accessibility and engages p53 transactivation. This in turn enforces cell cycle arrest and tumour suppression in TP53WT GBM. In line with these findings, BRD8 is highly expressed with H2AZ in proliferating single cells of patient-derived GBM, and is inversely correlated with CDKN1A, a canonical p53 target that encodes p21 (refs. 3,4). This work identifies BRD8 as a selective epigenetic vulnerability for a malignancy for which treatment has not improved for decades. Moreover, targeting the bromodomain of BRD8 may be a promising therapeutic strategy for patients with TP53WT GBM.
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The ChIP-seq and RNA-seq data generated in this study is available at the GEO database (https://www.ncbi.nlm.nih.gov/geo/) with accession number GSE158551. The RNA-seq data of GBM cells isolated from patient specimens are from datasets GSE84465 and GSE121720 in the GEO database.
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We thank H. Zheng at Weill Cornell Medical College for the mouse glioma cell lines and human brain-derived human stem cells; J. Sarkaria, A. C. M. Tuma and Z. Hu at Mayo Clinic for GBM patient-derived xenograft models; A. Schorn at CSHL for the original dual luciferase reporter plasmids; P. Filippakopoulos at the University of Oxford for helpful discussions on the bromodomain of BRD8; and members of the Mills and Vakoc laboratories for helpful discussions and suggestions over the course of this study. A.A.M. was supported by the National Cancer Institute of the National Institutes of Health under award number R01CA190997 and P30CA045508 and the Office Of The Director, National Institutes Of Health of the National Institutes of Health under award number R21OD018332. A.A.M. was also supported through the Darlene Carbone Brain Tumor Foundation, the Bradley Zankel Foundation, the Edward Davis Foundation, and the Cold Spring Harbor Laboratory–Northwell Health Affiliation. C.R.V. was supported by National Institutes of Health grant NCI R01 CA174793, NCI 5P01CA013106-Project 4, and the Cold Spring Harbor Laboratory and Northwell Health Affiliation. O.K. was supported by a Deutsche Forschungsgemeinschaft research fellowship (KL 3228/1-1). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
C.R.V. has received consulting fees from Flare Therapeutics, Roivant Sciences and C4 Therapeutics, has served on the advisory boards of KSQ Therapeutics, Syros Pharmaceuticals and Treeline Biosciences, has received research funding from Boehringer–Ingelheim and Treeline Biosciences, and owns a stock option from Treeline Biosciences.
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Extended data figures and tables
Extended Data Fig. 1 TP53 status in GBM and CRISPR screens in diverse cell types.
a, Pie charts showing frequency of TP53 mutation in cBioPortal GBM patient cohorts. b, Kaplan-Meier survival curve showing overall survival after first diagnosis of GBM patients with or without TP53 mutation. P value was calculated by Log-rank (Mantel-Cox) test. c, Systematic statistics of p53 mutations across all p53 codons, with the x-axis showing p53 codons with annotation of conserved domains across the protein shown below, and the y-axis showing the frequency of mutation at each codon. TP53 mutation data was compiled from the TCGA database and previous publications. d and e, RT-qPCR showing CDKN1A expression in the GBM cell lines used for CRISPR screens (d) and the primary patient-derived xenograft GBM cells used for validation (e), as compared with non-malignant human brain-derived neural stem cells (BNSC). Plotted is the relative expression level normalized to GAPDH as the mean ± s.d. (n = 3 biologically independent samples). f and g, MTT-based proliferation assays in the indicated GBM cell lines (f), primary patient cells and xenograft cells (g). Cells were treated with the MDM2 inhibitor Nutlin-3a, and were subjected to MTT assays after three population doublings (normalized to DMSO, n = 3 biologically independent samples). P values were calculated using two-tailed unpaired Student’s t-tests. h, Work flow of CRISPR screens. i, Comparison of domain-focused CRISPR screen in this study with genome-wide CRISPR screen data from the DepMap (https://depmap.org/portal/) using the same cell lines across diverse cancer types.
Extended Data Fig. 2 Validation of BRD8 as a p53-dependent vulnerability in GBM.
a, Summary of the sgRNAs used in this study targeting BRD8 exons encoding the bromodomain (sgBRD8-1 and sgBRD8-2) or introns (sgIntron-1 and sgIntron2) flanking the exons encoding the bromodomain. b, Western blots showing BRD8 depletion by two independent sgRNAs in the indicated cells. Data shown represents two independent results. sgNeg is a negative control. HSC70 serves as loading control. c, Cellular competition-based GFP dropout assays of individual sgRNAs targeting BRD8 and MDM2 along with sgNeg and a positive control sgRNA targeting the replication protein CDK1 (sgCDK1). Plotted is the percentage of independent GFP positive cells (normalized to P0, n = 3 biologically independent samples) at the indicated time points. P0 refers to day 3 after infection. d, Western blot showing BRD8 levels after targeting its introns by two independent sgRNAs (sgIntron-1 and sgIntron-2) (top) and GFP dropout assays along with sgNeg and sgCDK1 in A382WT cells (bottom). Plotted is the mean ± s.d. (normalized to P0, n = 3 biologically independent samples). e, Western blots showing BRD8 knockdown in A382WT cells transduced with two individual shRNAs targeting BRD8 (shBRD8-1 and shBRD8-2) (top) and GFP dropout assays in A382WT with shRluc as a negative control and shRPA3 as a positive control (bottom). Plotted is the mean ± s.d. (normalized to P0, n = 3 biologically independent samples). f, Design of CRISPR-resistant BRD8 cDNAs against sgBRD8-1 (BRD8 CR-1) or sgBRD8-2 (BRD8 CR-2). g, Western blots showing overexpression of CRISPR-resistant BRD8 cDNAs (BRD8 CR-1 and BRD8 CR-2) in the two indicated TP53WT GBM cells with empty vector as control (Ctrl). h and i, GFP dropout assays of sgNeg, sgCDK1, sgBRD8-1 and sgBRD8-2 in indicated TP53WT GBM cells expressing Ctrl or CRISPR-resistant BRD8 cDNAs (BRD8 CR-1 or BRD8 CR-2). Plotted is the mean ± s.d. (normalized to P0, n = 3 biologically independent samples). j, MTT-based proliferation assays in primary GBM patient cells, xenograft cells, and immortalized brain-derived neural stem cells (BNSC). Plotted is the mean ± s.d. (normalized to sgNeg, n = 3 biologically independent samples). P values were calculated using two-tailed unpaired Student’s t-tests. k, The top panel depicts the Aka luciferase-expressing construct used in orthotopic brain transplantation assays for non-invasive imaging in vivo. Bottom left: in vitro validation of luciferase activity in cultured cells using D-luc or AkaLuc-HCL substrates in empty control (Ctrl), Fluc-expressing (Fluc), and AkaLuc-expressing (AkaLuc) cells. Bottom right: Bioluminescence imaging of NOD SCID mice that had orthotopic brain transplantation of AkaLuc-expressing U87WT cells transduced with sgNeg or sgBRD8-2 (see correlating Kaplan-Meier survival plot, Fig. 1b). l and m, Kaplan-Meier survival plot of recipient mice that had been orthotopically transplanted with A382WT (l) or U251R273H (m) GBM cells expressing sgNeg or sgBRD8 into the brains of recipient mice. P value was calculated by Log-rank (Mantel-Cox) test.
Extended Data Fig. 3 BRD8 depletion activates p53-dependent cell cycle arrest and senescence in GBM.
a, Volcano plot of differentially expressed genes after BRD8 depletion. Fold change was calculated by averaging fold changes of two independent sgRNAs of BRD8 compared with sgNeg. Each sgRNA has two biological replicates. b, GSEA analysis showing significantly enriched p53-related proliferation and aging signatures after BRD8 depletion. c and d, RT-qPCR assay of proliferation-related genes after BRD8 depletion in A382WT (c) and patient-derived primary GBM cells (d). Plotted is the mean ± s.d. (n = 3 biologically independent samples). P values were calculated using two-tailed unpaired Student’s t-tests. e, Propidium Iodide (PI) staining and flow cytometry assays of A382WT cells after BRD8 loss (n = 3 biologically independent samples). f, SA-β-gal assay in A382WT cells. Data shown represents three independent results. Scale bar, 50 µm. g, GSEA plot of apoptosis signature after BRD8 depletion in A382WT cells. h, Annexin V staining and flow cytometry assay in A382WT cells. Plotted is the mean ± s.d. (n = 3 biologically independent samples). P values were calculated using two-tailed unpaired Student’s t-tests. i, RT-qPCR assay of apoptosis-related genes after BRD8 loss in A382WT cells. Plotted is the mean ± s.d. (n = 3 biologically independent samples). P values were calculated using two-tailed unpaired Student’s t-tests. j, RT-qPCR assay of CDKN1A expression in sgNeg or sgBRD8-2 expressing U251R273H and U118R213Q cells. Plotted is the mean ± s.d. (n = 3 biologically independent samples). P values were calculated using two-tailed unpaired Student’s t-tests. k, Western blot validating p53 knockdown by four different sgRNAs targeting TP53 in A382WT cells. Data shown represents three independent results. l, Western blot showing depletion efficiency of BRD8 and induction of p53 and p21 in Ctrl or p53-deficient A382WT cells. Data shown represents three independent results. HSC70 serves as a loading control. m, RT-qPCR assays of indicated cell cycle and senescence-related genes after transduction of sgNeg or sgBRD8-1 and sgBRD8-2 in Ctrl and p53-deficient A382WT cells. Plotted is the mean ± s.d. (n = 3 biologically independent samples). P values were calculated using two-tailed unpaired Student’s t-tests. n, SA-β-gal assays in Ctrl or p53-deficient A382WT cells after BRD8 loss. Data shown represents three independent results. Scale bar, 100 μM.
Extended Data Fig. 4 BRD8 reciprocally regulates transcription of p53 targets at a distinct level from MDM2.
a and b, GFP dropout assays of depleting BRD8 (sgBRD8-1 and sgBRD8-2) in Ctrl or MDM2 overexpression (MDM2OE) A382WT cells (a), and of depleting MDM2 (sgMDM2-1 and sgMDM2-2) in Ctrl or BRD8 overexpression (BRD8OE) A382WT cells (b). Plotted is the mean ± s.d. (n = 3 biologically independent samples). c and d, MTT assay of BRD8 depletion using sgBRD8-2 and targeting MDM2 using sgMDM2-2 (c) or the MDM2 inhibitor Nutlin-3a (d) separately or in combination in A382WT GBM cells. Plotted is the mean ± s.d. (n = 3 biologically independent samples). P values were calculated using two-tailed unpaired Student’s t-tests. e, Schematic of doxycycline-induced Flag-tagged p53 expression under the control of the tight TRE element (top), with validation of p53 induction by western blot assays (bottom). HSC70 serves as loading control. f, Volcano plot depicting genes that were significantly upregulated and downregulated greater than 1.5-fold after pP53 induction in A382WT cells. g, GSEA plots of p53 targets and GBM plasticity signatures after p53 induction (P53OE) in A382WT cells. h, Confocal microscopy in A382WT cells. Data shown represents three independent results. Scale bar, 25 µm. i, Western blot of BRD8 in empty vector control (Ctrl) and CRISPR-resistant N or C terminal Flag-tagged BRD8 (CR-2-N3F and CR-2-C3F)-expressing A382WT cells. j, GFP dropout assays of indicated sgRNAs in empty vector control (Ctrl), CR-2-N3F, and CR-2-C3F-expressing A382WT cells. Plotted is the mean ± s.d. (n = 3 biologically independent samples). k and l, Pie charts showing distribution of high-confidence peaks of BRD8 (k) and p53 (l) in A382WT cells. m, De novo binding motif of p53 derived from p53 ChIP-seq. E-value (expectancy value) represents the enrichment of the motif around the center of the peak binding regions using the binomial test. n, Venn diagram depicting overlapped genes located near high-confidence peaks of BRD8 and p53. o, Validation of BRD8 and p53 occupancy in a panel of common target loci using ChIP-qPCR. Plotted is data from two biological replicates. p, GSEA plot of p53-ChIPseq-targets signature derived from p53 ChIPseq after p53 induction (P53OE) in A382WT cells. q, Western blot showing depletion efficiency of p21 in A382WT cells. r, SA-β-gal assays of Ctrl or p21-deficient A382WT cells transduced with sgNeg or sgBRD8-2. Data shown represents three independent results. Scale bar, 50 µm. s and t, Pie charts depicting p53 mutation rate in low grade glioma (LGG) from TCGA Firehose Legacy (s), and CDKN1A expression in three subgroups divided based on TP53 status and BRD8 expression level in LGG (t). P values were calculated using two-tailed unpaired Student’s t-tests.
Extended Data Fig. 5 BRD8 is a subunit of the EP400 complex in GBM.
a, Western blot and silver staining of proteins immunoprecipitated by anti-Flag antibody in Flag-tagged BRD8-overexpressing or empty vector control (Ctrl) A382WT cells. Data shown represents three independent results. b, Summary of peptides detected by IP-MS in Flag-tagged BRD8 or Ctrl immunoprecipitates for 17 subunits of the EP400 complex. c, IP and western blots showing validation of core subunits of the EP400 complex in BRD8 immunoprecipitates. Data shown represents two independent results. HSC70 serves as loading control. d, Summary of specific and shared components of the EP400 and SRCAP complexes. Proteins pulled down by BRD8 are shown in dark blue text. e, RT-qPCR showing expression levels of EP400 and SRCAP in A382WT GBM cells. Plotted represents three biological replicates. f, Summary of GSEA analysis using P53OE up signature (genes significantly upregulated after p53 induction by doxycycline) after individual depletion of multiple components of the EP400 complex. Two independent sgRNAs were used for targeting each individual subunit, and sgNeg was used as control. g, Summary of GSEA analysis upon depletion of indicated components of the EP400 complex using the sgBRD8 up signature (genes significantly upregulated after BRD8 depletion by two independent sgRNAs and each sgRNA has two biological replicates. h, Schematic of the EP400 complex that occupies p53 target loci in GBM, with BRD8 being the most specific regulator.
Extended Data Fig. 6 BRD8 reprograms the p53 network through H2AZ.
a, Pie chart showing distribution of high-confidence peaks for H2AZ in A382WT cells. TTS, transcription termination sites. b, Density plots depicting H2AZ, BRD8, p53, H3K4me3, and H3K27ac enrichment surrounding the summit of high-confidence H2AZ peaks in A382WT cells, ranked by H2AZ peak intensity. c and d, Metaprofile comparing H3K4me3 (c) and H3K27ac (d) occupancy surrounding the summit of H3K4me3 and H3K27ac peaks, respectively, in A382WT cells transduced with sgRNA targeting BRD8 relative to negative control, sgNeg. The binding intensity is shown as sequencing depth normalized tag count. e, Gene tracks of BRD8 and p53, H2AZ, H3K4me3, and H3K27ac ChIP-seq occupancy after BRD8 depletion at co-targeted loci. f–h, ChIP-qPCR validation of occupancy of indicated proteins at the CDKN1A locus after BRD8 loss in A382WT cells (f), and two patient-derived primary GBM cells (g and h). Plotted represents the mean ± s.d. (n = 4 biologically independent samples). P values were calculated using two-tailed unpaired Student’s t-tests.
Extended Data Fig. 7 H2AZ phenocopies BRD8 in maintaining GBM proliferation.
a, Western blot showing depletion efficiency of H2AZ using two independent sgRNAs (sgH2AZ-1 and sgH2AZ-2) compared to a negative control (sgNeg). HSC70 serves as loading control. b, GFP dropout assays of sgNeg, sgCDK1 (a positive control), and sgH2AZ-1 and sgH2AZ-2 in A382WT cells. Plotted is the mean ± s.d. (n = 3 biologically independent samples). c, RT-qPCR assays of the indicated cell cycle and senescence-related genes after transduction of sgNeg, sgBRD8-1 and sgBRD8-2, or sgH2AZ-1 and sgH2AZ-2 in A382WT cells. Plotted is the mean ± s.d. (n = 3 biologically independent samples). P values were calculated using two-tailed unpaired Student’s t-tests. d, SA-β-gal assays of A382WT cells transduced with sgNeg, sgBRD8-2, or sgH2AZ-2. Scale bar, 50 µm. Data shown represents three independent results. e, GSEA plots after H2AZ depletion in A382WT cells using the upregulated (left) and the downregulated (right) gene signatures generated from RNA-seq profiling after BRD8 loss. f, GFP dropout assays of sgNeg, sgCDK1, sgRNAs targeting EP400 and H2AZ in the indicated cell lines. Plotted is the mean ± s.d. (n = 3 biologically independent samples). g, SA-β-gal assays in Ctrl or p53-deficient A382WT cells transduced with sgNeg, sgBRD8-2, or sgH2AZ-2. Data shown represents three independent results. Scale bar, 50 µm. h, RT-qPCR assays of indicated cell cycle and senescence-related genes after transduction of sgNeg, sgBRD8-2, or sgH2AZ-2 in Ctrl and p53-deficient A382WT cells. Plotted is the mean ± s.d. (n = 3 biologically independent samples). P values were calculated using two-tailed unpaired Student’s t-tests. i, GFP dropout assays of sgNeg, sgCDK1, and sgH2AZ-1 in Ctrl or two p21-deficient cells. Plotted is the mean ± s.d. (n = 3 biologically independent samples). P values were calculated using two-tailed unpaired Student’s t-tests.
Extended Data Fig. 8 The bromodomain of BRD8 is selectively essential in GBM.
a, Heat map showing CRISPR screen results for the entire family of bromodomain-containing proteins (classified into eight subgroups) in the indicated cancer types. b, Construction of the CRISPR resistant BRD8 cDNA against sgBRD8-2 tagged with 3XFlag (CR-2-C3F) and the bromodomain-deleted BRD8 cDNA tagged with 3XFlag (BDdel-C3F) (left). Expression is validated using western blot in A382WT cells (right). Data shown represents two independent results. HSC70 is a loading control. c, Confocal microscopy showing nuclear localization of both wild type (BRD8-C3F) and bromodomain deleted BRD8 (BDdel-C3F). Scale bar, 50 µm. Data shown represents three independent results.
Extended Data Fig. 9 The bromodomain of BRD8 sequesters H2AZ to restrain chromatin accessibility of intrinsic p53 to its targets.
a, Design of Proximity Ligation Assay (PLA) for detecting in situ proximal interactions between BRD8 and H2AZ. b, PLA showing interactions between BRD8 and H2AZ or H2AZac (acetylated H2AZ), using mouse Flag-M2 antibody against Flag-tagged BRD8 and rabbit antibody against H2AZ or H2AZac. Data shown represents three independent results. c, Immunoprecipitation followed by western blotting to detect interactions between H2AZ or H2AZac, and Flag-tagged wild type BRD8 (BRD8-C3F) or bromodomain deleted BRD8 (BDdel-C3F) in A382WT cells, respectively. Data shown represents two independent results. d, Construction (left) and expression (right) of recombinant GST fusion BRD8 proteins. e and f, Western blot and Coomassie blue staining of purified recombinant GST fusion BRD8 proteins. g, In vitro pulldowns and western blots showing interaction of the BD of BRD8 (Upper) and full length of BRD8 (Lower) with H2AZ and H2AZac. Data shown represents three independent results. h, Gene tracks depicting occupancy of BRD8, p53, H2AZ, H3K27ac, H3K4me3 and chromatin accessibility by ATAC-seq in control (sgNeg), BRD8- or H2AZ-depleted A383WT GBM cells. i–k, RT-qPCR assays validating enhanced chromatin accessibility at the CDKN1A promoter region after depletion of BRD8 (sgBRD8) and H2AZ (sgH2AZ) compared with control (sgNeg) in A382WT GBM (i) and two patient-derived primary GBM cells MN03WT (j) and MN06WT(k). Plotted is the mean ± s.d. (n = 3 biologically independent samples). P values were calculated using two-tailed unpaired Student’s t-tests. l and m, Western blot showing expression of indicated proteins at different timepoints following BRD8 knockdown (l) and multiple modifications of p53 at day 5 (m) in A382WT GBM cells. Data shown represents three independent results.
Extended Data Fig. 10 BRD8 and H2AZ are highly expressed in KI67-positive cells of GBM patients.
a, H&E and IHC staining for BRD8 and H2AZ in normal human tissues, including brain (I), spleen (ii), lymph (iii), lung (iv), liver (v), and tonsil (vi). Scale bar, 50 µm. b, Protein expression levels of the EP400 components across diverse foetal tissues, adult tissues, and hematopoietic cells. Heat map represents log2 value of raw data compiled from the human proteome. c, IHC staining showing expression of BRD8, H2AZ, and the proliferation marker KI67. The bottom panels show an overview at low magnification (scale bar, 5 mm), while the top panels are higher magnification views (scale bar, 400 µm) showing typical features of GBM, including pseudopalisades (along red-dashed lines, highly proliferating cells with strong staining of BRD8, H2AZ, and KI67), necrosis (black arrowheads), vascularity/neoangiogenesis (blue arrowheads), and high nuclear atypia. d, H&E and IHC staining for KI67, BRD8, and H2AZ using the representative GBM patient specimen with adjacent lower grade ((i), (iii), (v), (vii)) and highly aggressive regions ((ii), (iv), (vi), (viii)). The upper panels show low magnification (scale bar, 1mm), and two enlarged fields (scale bar, 100 µm) with adjacent lower grade and high-grade phenotypes shown below. The percentage scores are from three different areas for each phenotypic category. Plotted is mean ± s.d. P values were calculated using two-tailed unpaired Student’s t-tests. e and f, Plotted is mean ± s.d. for the percentage scores of KI67, H2AZ, and BRD8 from three different areas within each phenotypic category in patient specimens TDPG947 TP53WT(e) and TDPG1251 TP53WT(f). P values were calculated using two-tailed unpaired Student’s t-tests. g, Heatmap depicting expression of proliferation-related genes (ranked by p value) in BRD8Low and BRD8High GBM cells (columns). h, Comparison of MKI67, H2AFV, CDKN1A gene expression between BRD8Low and BRD8High subgroups in GBM cells. HIST1H2AG gene serves as a control. i, Overlap of positively (Pos) or negatively (Neg) associated proliferation-related genes with BRD8 expression levels in datasets GSE84465 and GSE121720, respectively.
This file contains Supplementary Figs. 1–8.
Supplementary Table 1
Combined tables summarizing TP53 mutations in GBM. Related to Fig. 1 and Extended Data Fig. 1.
Supplementary Table 2
Combined tables for domain-focused CRISPR screens and exon tiling of BRD8 data. Related to Figs. 1 and 3 and Extended Data Figs. 1 and 8.
Supplementary Table 3
BRD8 IP–MS data. Related to Fig. 2 and Extended Data Fig. 5.
Supplementary Table 4
Combined tables for immunohistochemistry staining scores of BRD8, H2AZ and KI67 in TMAs and individual specimens from Stanford University (Stanford), the Mayo Clinic (Mayo) and Northwell Health (Northwell). Related to Fig. 4 and Extended Data Fig. 10.
Supplementary Table 5
Combined tables for bulk and single-cell transcriptional expression data from TCGA and the GEO database (GSE84465 and GSE121720). Related to Figs. 1 and 4 and Extended Data Fig. 10.
Supplementary Table 6
Combined tables for oligonucleotides used in this study. The oligonucleotides include domain-focused sgRNA library, exon-tiling sgRNA library, sgRNA sequences targeting the EP400 complex and p53 pathway, primers for qPCR with reverse transcription, ChIP–qPCR primers, shRNA primers and primers used for library preparation. Related to all figures.
Supplementary Table 7
Combined tables for antibodies, bacterial strains, chemicals, crucial commercial assay kits, model cell lines, recombinant DNAs and software and algorithms used in this study. Related to all figures.
Supplementary Table 8
Combined tables of source data for cellular competition-based GFP dropout assays, qPCR with reverse transcription assays, ChIP–qPCR assays, MTT assays, flow cytometry assays for cell cycle and apoptosis, orthotopic brain transplantation experiments, percentage scores of BRD8, H2AZ and KI67 in immunohistochemistry staining. Related to all figures.
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Sun, X., Klingbeil, O., Lu, B. et al. BRD8 maintains glioblastoma by epigenetic reprogramming of the p53 network. Nature 613, 195–202 (2023). https://doi.org/10.1038/s41586-022-05551-x
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