Genome-wide localization of SMAD2/3 and JUN family protein and epigenetic landscapes in human breast cell line treated with or without TGF-β.

The non-receptor tyrosine kinase SRC is overexpressed in various human cancers, however, transcriptional mechanisms underlying SRC expression is poorly understood. In this study, we found that transforming growth factor-β (TGF-β), which is abundantly secreted in tumor microenvironment, upregulates SRC protein and mRNA expression. To clarify the molecular mechanisms underlying TGF-β-induced SRC expression, we analyzed the genome-wide localization of SMAD2/3 and JUN family protein and epigenetic landscapes in human breast cell lines. These results showed that a novel TGF-β-responsive enhancer, which localizes at intragenic region of SRC, is activated via TGF-β/SMAD pathway and upregulates SRC expression. Chromatin immunoprecipitation and DNA sequencing (ChIP-Seq) for H3K4me3, H3K27Ac, SMAD2, SMAD3, JUN, and JUNB in MCF10A and H3K27Ac in BT-549. Cells were treated with or without TGF-β (10 ng/ml) for 24h.