Data from Yin Yang 1 Regulates the Expression of <i>Snail</i> through a Distal Enhancer

Abstract

<div>Abstract<p>Expression of the <i>Snail</i> gene is required for the epithelial-mesenchymal transitions that accompany mammalian gastrulation, neural crest migration, and organ formation. Pathologic expression of <i>Snail</i> contributes to the migratory capacity of invasive tumors, including melanomas. To investigate the mechanism of <i>Snail</i> up-regulation in human melanoma cells, a conserved enhancer located 3′ of the <i>Snail</i> gene was analyzed. An overlapping Ets and yin yang 1 (YY1) consensus sequence, in addition to a SOX consensus sequence, was required for full enhancer activity. Proteins specifically binding these sequences were detected by electrophoretic mobility shift assay. The Ets/YY1 binding activity was purified by DNA-affinity chromatography and identified as YY1. Although ubiquitously expressed, YY1 was bound at the <i>Snail</i> 3′ enhancer <i>in vivo</i> in <i>Snail</i>-expressing cells but not in cells that did not express <i>Snail</i>. Knockdown of YY1 in A375 cells led to decreased <i>Snail</i> expression. These results identify a role for YY1 in regulating transcription of <i>Snail</i> in melanoma cells through binding to the <i>Snail</i> 3′ enhancer. (Mol Cancer Res 2009;7(2):221–9)</p></div>