Project description:Approximately 50% of prostate cancers have chromosomal translocations resulting in the over-expression one of four ETS family transcription factors. However, it is not known why these four four family members are selected for oncogenic roles, while other ETS proteins are not. We found that the four oncogenic ETS family members have a specific role in prostate cell migration. Using chromatin immunoprecipitation coupled with next-generation sequencing, this specific biological function was matched to a specific set of genomic targets highlighted by the presence of an AP-1 binding site. ETS/AP-1 binding sites are prototypical Ras-responsive elements, but oncogenic ETS proteins could activate a Ras/MAPK transcriptional program in the absence of MAPK activation. These findings indicate that the specific function of ETS proteins over-expressed in prostate cancer is the activation of a Ras/MAPK gene expression program in the absence of signaling pathway mutations. ChIP sequencing two transcription factors in PC3 cells, four transcription factors plus a FLAG control in RWPE-1 cells and input DNA sequencing from each cell line.
Project description:The ETS transcription factor ELF5 drives mammary alveolar development in preparation for lactation by forcing differentiation within the progenitor cell population. In luminal A breast cancer, early disease progression is predicted by high levels of ELF5, and in preclinical models elevated ELF5 is associated with its two key features, the acquisition of resistance to endocrine therapy and increased metastasis. Here we demonstrate using chromatin immunoprecipitation sequencing that ELF5 binding overlaps with FOXA1 and ER at enhancers and promoters, and when elevated causes FOXA1 and ER to bind to new regions of the genome involved in resistance to endocrine therapy.
