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First published online July 1, 2009

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Power struggle at an integrin promoter

The integrin 6β4 – which functions as a cell-surface receptor for laminins of the basement membrane – is expressed predominantly in epithelial cells and in some carcinomas. Despite the role of 6β4 integrin in tumour-cell behaviour, little has been known about how expression of the β4 subunit is regulated. Now, though, Arthur Mercurio and colleagues (p. 2473) explore the role of epigenetic modifications on β4 expression, and show that the β4 promoter (which contains a large CpG island) is unmethylated in mammary-gland basal epithelial cells (which express β4) and methylated in luminal epithelial cells from the same tissue (which do not). In addition, when mammary-gland cells are treated with TGFβ to induce the epithelial-mesenchymal transition (EMT), β4 expression is lost and the promoter is methylated de novo. At the same time, they report, there is a dramatic decrease in the levels of histone modifications that are associated with actively transcribed promoters, and an increase in the level of a repressive histone modification. When TGFβ is withdrawn, β4 expression is restored; interestingly, this involves partial reversal of EMT-induced histone modifications in the promoter, but does not require demethylation. The authors conclude that histone modifications, not methylation status, are the predominant factor in reactivating β4-integrin expression in this context.

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Related articles in JCS:

Regulation of β4-integrin expression by epigenetic modifications in the mammary gland and during the epithelial-to-mesenchymal transition

Xiaofang Yang, Bryan Pursell, Shaolei Lu, Tsun-Kai Chang, and Arthur M. Mercurio
JCS 2009 122: 2473-2480. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Social Bookmarking                         What's this?