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    Id2 complexes with the SNAG domain of Snai1 inhibiting Snai1-mediated repression of integrin beta4

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    Authors
    Chang, Cheng
    Yang, Xiaofang
    Pursell, Bryan
    Mercurio, Arthur M.
    UMass Chan Affiliations
    Department of Cancer Biology
    Document Type
    Journal Article
    Publication Date
    2013-10-01
    Keywords
    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
    Amino Acids, Peptides, and Proteins
    Cancer Biology
    Cell Biology
    Developmental Biology
    Molecular Biology
    Neoplasms
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    Abstract
    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.00434-13
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/26303
    PubMed ID
    23878399
    Related Resources

    Link to Article in PubMed

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    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
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