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dc.contributor.authorCakouros, D.en
dc.contributor.authorIsenmann, S.en
dc.contributor.authorCooper, L.en
dc.contributor.authorZannettino, A.en
dc.contributor.authorAnderson, P.en
dc.contributor.authorGlackin, C.en
dc.contributor.authorGronthos, S.en
dc.identifier.citationMolecular and Cellular Biology, 2012; 32(8):1433-1441en
dc.description.abstractThe main impairment to tissue maintenance during aging is the reduced capacity for stem cell self-renewal over time due to senescence, the irreversible block in proliferation. We have previously described that the basic helix-loop-helix (bHLH) transcription factor Twist-1 can greatly enhance the life span of bone marrow-derived mesenchymal stem/stromal cells (MSCs). In the present study, we show that Twist-1 potently suppresses senescence and the Ink4A/Arf locus with a dramatic decrease in the expression of p16 and to some extent a decrease in p14. Furthermore, the polycomb group protein and histone methyltransferase Ezh2, which suppresses the Ink4A/Arf locus, was found to be induced by Twist-1, resulting in an increase in H3K27me3 along the Ink4A/Arf locus, repressing transcription of both p16/p14 and senescence of human MSCs. Furthermore, Twist-1 inhibits the expression of the bHLH transcription factor E47, which is normally expressed in senescent MSCs and induces transcription of the p16 promoter. Reduced Twist-1 wild-type expression and function in bone cells derived from Saethre-Chotzen patients also revealed an increase in senescence. These studies for the first time link Twist-1 to histone methylation of the Ink4A/Arf locus by controlling the expression of histone methyltransferases as well as the expression of other bHLH factors.en
dc.description.statementofresponsibilityDimitrios Cakouros, Sandra Isenmann, Lachlan Cooper, Andrew Zannettino, Peter Anderson, Carlotta Glackin, and Stan Gronthosen
dc.publisherAmer Soc Microbiologyen
dc.rightsCopyright © 2012, American Society for Microbiology. All Rights Reserved.en
dc.subjectCells, Cultured; Mesenchymal Stem Cells; Humans; Histone-Lysine N-Methyltransferase; DNA-Binding Proteins; Nuclear Proteins; Histones; Transcription Factors; Gene Expression Regulation; Epigenesis, Genetic; Methylation; Adult; Cyclin-Dependent Kinase Inhibitor p16; Polycomb Repressive Complex 2; Twist-Related Protein 1; Enhancer of Zeste Homolog 2 Protein; Cellular Senescence; Histone Methyltransferasesen
dc.titleTwist-1 Induces Ezh2 Recruitment Regulating Histone Methylation along the Ink4A/Arf Locus in Mesenchymal Stem Cellsen
dc.typeJournal articleen
pubs.library.collectionMicrobiology and Immunology publicationsen
dc.identifier.orcidCakouros, D. [0000-0001-6136-0761]en
dc.identifier.orcidZannettino, A. [0000-0002-6646-6167]en
dc.identifier.orcidAnderson, P. [0000-0002-3730-4652]en
dc.identifier.orcidGronthos, S. [0000-0002-6225-3084]en
Appears in Collections:Microbiology and Immunology publications

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