Transcriptional regulation by TES and TEAD1 in SNB19 glioblastoma cells: RNA-seq

This study investigates transcriptional regulation by TES (TEAD1 Epigenetic Silencer, an engineered epigenetic silencer factor targeting the YAP/TAZ-TEAD axis) in SNB19 glioblastoma cells using RNA-seq. TES was engineered by fusing the KRAB domain, the catalytic domain of DNMT3A together with DNMT3L, and the N-terminal 166 amino acids of TEAD1. RNA-seq was performed 48 hours after lentiviral transduction to identify differentially expressed genes upon TES expression compared to GFP control in three biological replicates per condition. TES expression induced widespread transcriptional repression of YAP/TAZ-dependent gene programs, with downregulated genes enriched for cell-cycle regulation and TEAD family transcription factor binding sites. Overall design: RNA-seq profiling of SNB19 glioblastoma cells expressing TES (a synthetic TEAD1-targeting transcriptional silencer) versus GFP control. Three biological replicates per condition (6 samples total).

本研究以SNB19胶质母细胞瘤细胞为模型，探究TES（TEAD1表观遗传沉默因子，一种靶向YAP/TAZ-TEAD轴的工程化表观遗传沉默因子）介导的转录调控，采用RNA-seq（RNA测序）开展分析。TES通过融合KRAB结构域、DNMT3A的催化结构域与DNMT3L，以及TEAD1的N端166个氨基酸构建得到。于慢病毒转导48小时后进行RNA-seq检测，对比TES表达组与GFP对照组的差异表达基因，每组设置3次生物学重复。实验结果表明，TES表达可广泛抑制YAP/TAZ依赖的基因程序，下调基因显著富集于细胞周期调控通路及TEAD家族转录因子结合位点相关区域。总体实验设计：对表达TES（一种合成的TEAD1靶向转录沉默因子）的SNB19胶质母细胞瘤细胞与GFP对照组开展RNA-seq分析，每组设置3次生物学重复，共计6个样本。