KLF5 interacts with RUVBL1/2 to activate classical and basal lineage identities in PDAC [ChIP-seq]

We identify KLF5 as a lineage master regulator and a dependency in classical and basal subtypes of human PDAC. We integrate proteomic and genetic screens to reveal RUVBL1 and RUVBL2 as transcriptional coactivators of KLF5 in PDAC. We use biochemical and epigenomic methods to validate that KLF5-RUVBL1/2 complexes directly activate lineage identity genes in PDAC. Overall design: ChIP-seq of KLF5 and RUVBL1/2 in basal-like and classical human pancreatic cancer cell lines.

我们鉴定出KLF5（Krüppel样转录因子5）为人类胰腺导管腺癌（PDAC，Pancreatic Ductal Adenocarcinoma）经典型与基底样亚型的谱系主调控因子及细胞依赖性基因。我们整合蛋白质组学与遗传筛选实验，揭示RUVBL1与RUVBL2是PDAC中KLF5的转录共激活因子。我们借助生化与表观基因组学手段验证，KLF5-RUVBL1/2复合物可直接激活PDAC中的谱系特征基因。实验整体设计：在基底样型与经典型人类胰腺癌细胞系中开展KLF5、RUVBL1及RUVBL2的染色质免疫沉淀测序（ChIP-seq，Chromatin Immunoprecipitation sequencing）。