转录激活的RCOR2 neo-TADs RELA室管膜瘤。在重建ZFTA肿瘤基因组染色质联系人(示例4 ep53)包括串联重复导致ZFTA-RELA融合(chr1:63532174 - 65429788、绿色框)。固体黑匣子显示TADs被应用TopDom高c数据映射到重建肿瘤基因组,包括neo-TAD横跨DNA断点。b, c重建基因组含有ZFTA-RELA融合基因位点在ZFTA室管膜瘤样例4 ep53 (b)和11 ep22 (c)。黑匣子/三角形表明TADs报道TopDom当应用于重建肿瘤基因组。neo-TAD是确定的,它跨越了DNA断点和地方RCOR2成新的监管环境。d箱线图RCOR2基因表达在使用Affymetrix室管膜瘤组(n = 393)的基因表达数据。RCOR2显著调节ZFTA肿瘤(ZFTA与其他肿瘤类limma p-val。:7.62 e−27)。中线,框限制,胡须,表明中值,上/下四分位数,分别1.5×四分位范围和异常值。e RCOR2之间的相关性和ZFTA ZFTA(左侧,n = 76,软木= 0.663,p-val e = 6.93−11)和PFA室管膜瘤样本(右侧,n = 200,软木= 0.336 p-val = 1.13 e−06)。外:我shRNA时间进程混战ZFTA实验(EP1NS)和PFA (EPD210FH)室管膜瘤细胞系使用紧急控制和两个成分构造目标要么RCOR2 EP1NS (f),在EPD210FH RCOR2 (g),在EP1NS LSD1 (h)与LSD1 EPD210FH (i)。所有构造GFP标记和GFP阳性细胞是按流式细胞仪。 For panel (f), error bars represent mean ± SD for n = 3 independent experiments (two-tailed paired t test p-val = 0.0018 and 0,0046; shRCOR#1 and shRCOR2#2, respectively). For panels (g–i), normalized data represent mean from n = 2 independent experiments per cell line. j, k Dose–response curves of single-compound treatment with ORY-1001 (j) or Entinostat (k) of ZFTA (EP1NS, BT165 and ST-1) and PFA (EPD210FH, BT214) ependymoma spheroids over a 72-h time-course using Celltiter-Glo cell viability assays. For each sample the results are presented as percentage of the Luminescence signal from control condition (i.e. water for ORY-1001 and DMSO for Entinostat). Error bars represent mean ± SD for n = 3 independent experiments (one-way ANOVA test p-val < 0,0001). Credit:自然通讯(2023)。DOI: 10.1038 / s41467 - 023 - 38044 - 0