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Type: Journal article
Title: Twist-1 Induces Ezh2 Recruitment Regulating Histone Methylation along the Ink4A/Arf Locus in Mesenchymal Stem Cells
Author: Cakouros, D.
Isenmann, S.
Cooper, L.
Zannettino, A.
Anderson, P.
Glackin, C.
Gronthos, S.
Citation: Molecular and Cellular Biology, 2012; 32(8):1433-1441
Publisher: Amer Soc Microbiology
Issue Date: 2012
ISSN: 0270-7306
Statement of
Dimitrios Cakouros, Sandra Isenmann, Lachlan Cooper, Andrew Zannettino, Peter Anderson, Carlotta Glackin, and Stan Gronthos
Abstract: The 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.
Keywords: Cells, Cultured
Mesenchymal Stem Cells
Histone-Lysine N-Methyltransferase
DNA-Binding Proteins
Nuclear Proteins
Transcription Factors
Gene Expression Regulation
Epigenesis, Genetic
Cyclin-Dependent Kinase Inhibitor p16
Polycomb Repressive Complex 2
Twist-Related Protein 1
Enhancer of Zeste Homolog 2 Protein
Cellular Senescence
Histone Methyltransferases
Rights: Copyright © 2012, American Society for Microbiology. All Rights Reserved.
DOI: 10.1128/MCB.06315-11
Appears in Collections:Aurora harvest
Microbiology and Immunology publications

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