Identifying FOXA1-GR transcriptional targets in FOXA1-GR dependent NSCLC

The FOXA1 pioneer factor is an essential mediator of steroid receptor function in multiple hormone dependent cancers, including breast and prostate cancers, enabling nuclear receptors such as ER and AR to activate lineage specific growth programs. . Analyzing data from loss-of-function screens, we identified a subset of NSCLC tumor lines where proliferation is FOXA1-dependent. Using rapid immunoprecipitation and mass spectrometry of endogenous protein (RIME) we identified chromatin-localized interaction between FOXA1 and glucocorticoid receptor (GR) in these tumor cells. Knockdown of GR inhibited proliferation of FOXA1-dependent, but not FOXA1-independent NSCLC cells. Here, we utilized ChIP-sequencing to identify a permissive set of genes potentially regulated by FOXA1 and GR to understand potential mechanisms underlying FOXA1-GR dependence in NSCLC. Overall design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) to map overlapping binding regions of Glucocorticoid receptor (GR) and FOXA1, as well as the histone modification H3K27ac, with and without GR ligand stimulation in NCI-H441 cells.