Department of Cancer Biology
Animals; Base Sequence; Binding Sites; Cadherins; Cell Line; Epithelial-Mesenchymal Transition; Gene Expression Profiling; Gene Expression Regulation; Histones; Humans; Inhibitor of Differentiation Protein 2; Integrin beta4; Lysine; MCF-7 Cells; Methylation; Mice; Molecular Sequence Data; Oligonucleotide Array Sequence Analysis; Promoter Regions, Genetic; Protein Binding; RNA Interference; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Nucleic Acid; Transcription Factors; Transforming Growth Factor beta1
Cancer Biology | Cell Biology | Developmental Biology | Molecular Biology | Neoplasms
The epithelial-mesenchymal transition (EMT) is a fundamental process that underlies development and cancer. Although the EMT involves alterations in the expression of specific integrins that mediate stable adhesion to the basement membrane, such as alpha6beta4, the mechanisms involved are poorly understood. Here, we report that Snai1 inhibits beta4 transcription by increasing repressive histone modification (trimethylation of histone H3 at K27 [H3K27Me3]). Surprisingly, Snai1 is expressed and localized in the nucleus in epithelial cells, but it does not repress beta4. We resolved this paradox by discovering that Id2 complexes with the SNAG domain of Snai1 on the beta4 promoter and constrains the repressive function of Snai1. Disruption of the complex by depleting Id2 resulted in Snai1-mediated beta4 repression with a concomitant increase in H3K27Me3 modification on the beta4 promoter. These findings establish a novel function for Id2 in regulating Snai1 that has significant implications for the regulation of epithelial gene expression.
Rights and Permissions
Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.
DOI of Published Version
Mol Cell Biol. 2013 Oct;33(19):3795-804. doi: 10.1128/MCB.00434-13. Epub 2013 Jul 22.Link to article on publisher's site
Molecular and cellular biology
Chang, Cheng; Yang, Xiaofang; Pursell, Bryan; and Mercurio, Arthur M., "Id2 complexes with the SNAG domain of Snai1 inhibiting Snai1-mediated repression of integrin beta4" (2013). Cancer Biology Publications and Presentations. 219.