S100A8/S100A9 cytokine functions as transcriptional coactivator during breast cellular transformation

In an inducible model of human breast cellular transformation, we map genome-wide chromatin binding of S100A8, S100A9 and Pol II. We show that the calcium-dependent cytokines S100A8 and S100A9 are recruited to numerous promoters and enhancers. This recruitment is associated with multiple DNA sequence motifs recognized by DNA-binding transcription factors that are linked to transcriptional activation and are important for transformation. Nuclear-specific expression of S100A8/A9 promotes oncogenic transcription and leads to enhanced breast transformation phenotype. These results suggest that, in addition to its classical cytokine function, S100A8/A9 can act as a transcriptional co-activator. ChIP-seq for S100A8-Flag, S100A9-Flag, or Pol II in non-transformed (EtOH-treated) and transformed (TAM-trated) MCF10A cells expressing ER-Src, a fusion between the v-Src oncoprotein and the ligand-binding domain of estrogen receptor