Homo sapiens

BACKGROUND Transient induction of the Src oncoprotein in a non-transformed breast cell line can initiate an epigenetic switch to a cancer cell via a positive feedback loop that involves activation of the STAT3 and NF-?B transcription factors. RESULTS Here we show that during the transformation process, nucleosome-depleted regions (defined by FAIRE) are largely unchanged, and that both before and during transformation STAT3 binds almost exclusively to previously open chromatin regions. Roughly a third of the transformation-inducible genes require STAT3 for the induction. STAT3 and NF-?B appear to drive the regulation of different gene sets during the transformation process. Interestingly, STAT3 directly regulates the expression of NFKB1, which encodes a subunit of NF-kB, and IL6, a cytokine that stimulates STAT3 activity. Lastly, many STAT3 binding sites are also bound by FOS, and expression of several AP-1 factors is altered during transformation in a STAT3-dependent manner, suggesting that STAT3 may co-operate with AP-1 proteins. CONCLUSIONS These observations uncover additional complexities to the inflammatory feedback loop that are likely to contribute to the epigenetic switch. In addition, our data suggest that gene expression changes during transformation, whether driven by pre-existing or induced transcription factors, occur largely through preexisting nucleosome-depleted regions.