Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements

Aging Cell - Tập 12 Số 2 - Trang 247-256 - 2013
Marco De Cecco1, Steven W. Criscione2, Edward Peckham2, Sara Hillenmeyer2, Eliza A. Hamm2, Jayameenakshi Manivannan2, Adam Peterson2, Jill A. Kreiling2, Nicola Neretti2, John M. Sedivy2
1Department of Molecular Biology, Cell Biology and Biochemistry, Center for Genomics and Proteomics, Brown University, Providence, RI 02912, USA.
2Department of Molecular Biology, Cell Biology and Biochemistry, Center for Genomics and Proteomics Brown University Providence 02912 RI USA

Tóm tắt

SummaryReplicative cellular senescence is an important tumor suppression mechanism and also contributes to aging. Progression of both cancer and aging include significant epigenetic components, but the chromatin changes that take place during cellular senescence are not known. We used formaldehyde assisted isolation of regulatory elements (FAIRE) to map genome‐wide chromatin conformations. In contrast to growing cells, whose genomes are rich with features of both open and closed chromatin, FAIRE profiles of senescent cells are significantly smoothened. This is due to FAIRE signal loss in promoters and enhancers of active genes, and FAIRE signal gain in heterochromatic gene‐poor regions. Chromatin of major retrotransposon classes, Alu, SVA and L1, becomes relatively more open in senescent cells, affecting most strongly the evolutionarily recent elements, and leads to an increase in their transcription and ultimately transposition. Constitutive heterochromatin in centromeric and peri‐centromeric regions also becomes relatively more open, and the transcription of satellite sequences increases. The peripheral heterochromatic compartment (PHC) becomes less prominent, and centromere structure becomes notably enlarged. These epigenetic changes progress slowly after the onset of senescence, with some, such as mobilization of retrotransposable elements becoming prominent only at late times. Many of these changes have also been noted in cancer cells.

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Aging Cell

Tập 12 Số 2

247-256

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