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dc.contributor.authorCakouros, D.-
dc.contributor.authorIsenmann, S.-
dc.contributor.authorCooper, L.-
dc.contributor.authorZannettino, A.-
dc.contributor.authorAnderson, P.-
dc.contributor.authorGlackin, C.-
dc.contributor.authorGronthos, S.-
dc.identifier.citationMolecular and Cellular Biology, 2012; 32(8):1433-1441-
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.-
dc.description.statementofresponsibilityDimitrios Cakouros, Sandra Isenmann, Lachlan Cooper, Andrew Zannettino, Peter Anderson, Carlotta Glackin, and Stan Gronthos-
dc.publisherAmer Soc Microbiology-
dc.rightsCopyright © 2012, American Society for Microbiology. All Rights Reserved.-
dc.subjectCells, Cultured-
dc.subjectMesenchymal Stem Cells-
dc.subjectHistone-Lysine N-Methyltransferase-
dc.subjectDNA-Binding Proteins-
dc.subjectNuclear Proteins-
dc.subjectTranscription Factors-
dc.subjectGene Expression Regulation-
dc.subjectEpigenesis, Genetic-
dc.subjectCyclin-Dependent Kinase Inhibitor p16-
dc.subjectPolycomb Repressive Complex 2-
dc.subjectTwist-Related Protein 1-
dc.subjectEnhancer of Zeste Homolog 2 Protein-
dc.subjectCellular Senescence-
dc.subjectHistone Methyltransferases-
dc.titleTwist-1 Induces Ezh2 Recruitment Regulating Histone Methylation along the Ink4A/Arf Locus in Mesenchymal Stem Cells-
dc.typeJournal article-
dc.identifier.orcidCakouros, D. [0000-0001-6136-0761]-
dc.identifier.orcidZannettino, A. [0000-0002-6646-6167]-
dc.identifier.orcidAnderson, P. [0000-0002-3730-4652]-
dc.identifier.orcidGronthos, S. [0000-0002-6225-3084]-
Appears in Collections:Aurora harvest
Microbiology and Immunology publications

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