Chromatin Looping Shapes KLF5-Dependent Transcriptional Programs in Human Epithelial Cancers.

ABSTRACT: Activation of transcription factors is a key driver event in cancer. We and others have recently reported that the Krüppel-like transcription factor KLF5 is activated in multiple epithelial cancer types including squamous cancer and gastrointestinal adenocarcinoma, yet the functional consequences and the underlying mechanisms of this activation remain largely unknown. Here we demonstrate that activation of KLF5 results in strongly selective KLF5 dependency for these cancer types. KLF5 bound lineage-specific regulatory elements and activated gene expression programs essential to cancer cells. HiChIP analysis revealed that multiple distal KLF5 binding events cluster and synergize to activate individual target genes. Immunoprecipitation-mass spectrometry assays showed that KLF5 interacts with

SUBMITTER: Liu Y 

PROVIDER: S-EPMC7787512 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature