Id2 complexes with the SNAG domain of Snai1 inhibiting Snai1-mediated repression of integrin beta4
UMass Chan Affiliations
Department of Cancer BiologyDocument Type
Journal ArticlePublication Date
2013-10-01Keywords
AnimalsBase 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
Amino Acids, Peptides, and Proteins
Cancer Biology
Cell Biology
Developmental Biology
Molecular Biology
Neoplasms
Metadata
Show full item recordAbstract
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.Source
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
DOI
10.1128/MCB.00434-13Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26303PubMed ID
23878399Related Resources
Rights
Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.
ae974a485f413a2113503eed53cd6c53
10.1128/MCB.00434-13