Mammary epithelial cells need a laminin-rich extracellular matrix (ECM) to achieve a functionally differentiated phenotype that includes secretion of milk-specific proteins such as beta-casein. There is good evidence that ECM-induced expression of beta-casein involves an 'ECM-response element' in the promoter of the casein gene that is activated by integrin-mediated signalling. This article proposes that ECM-induced structural changes in the cytoskeleton, histone organization and the nuclear matrix contribute to this tissue-specific gene expression.