Study Links Epigenetics, Aging, Mutations in Nuclear Proteins to Better Understand Cancer, Rare Disorders

Epigenetic factors  act on the structures in which genes reside, called chromatin. Scientists at the Perelman School of Medicine at the University of Pennsylvania found that senescent cells appear to undergo changes in their chromatin.  They found similar changes in cells that are prematurely aging. These changes take place inside the chromatin of a cell?s nucleus. In the chromatin, DNA is wound around proteins called histones. Enzymes called histone modifiers mark the chromatin ? like using sticky notes as reminders ? to open up or close down regions of the genome, which makes these areas more or less available to be read as a gene.

The scientists, including Shelley Berger, PhD, professor of Cell and Developmental Biology at the Perelman School of Medicine at the University of Pennsylvania and Parisha Shah, PhD, a postdoctoral fellow in the Berger lab, compared differences in the presence of the genome-wide sticky notes between two lung cell populations, one at the start of proliferation, as a control, and the other at the end of its replication cycle and senescent. Their study, which also included scientists from the Institute of Cancer Sciences, University of Glasgow, UK and the Department of Biology, Penn Genome Frontiers Institute, was, in part, supported by the National Institute on Aging and the Ellison Medical Foundation.

Fig. 1 – When comparing gains and losses of two histone modifications, there were large-scale domains of enriched histone modifier mesas and depleted histone modifier canyons, as graphically depicted when comparing the gains and losses. The enriched mesas form at lamin B1-associated areas on the chromatin.

Fig. 2 – The lamina, a network lining the inside of the membrane of the nucleus. It provides support to keep the shape of the nucleus and also regulates DNA replication by making some areas of the genome less (restricted) or more (permissive) available to be translated into proteins. In the case of silencing genes, the proteins of the lamina do this by creating tight connections between parts of the chromatin and the nuclear membrane.

For more information:
[1] Shah PP, Donahue G, Otte GL, Capell BC, Nelson DM, Cao K, Aggarwala V, et al. Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape.Genes Dev. 2013 Aug 15;27(16):1787-99. doi: 10.1101/gad.223834.113. Epub 2013 Aug 9. [Article][PubMed]
[2] Epigenetic Factors Play a Role in Cell Senescence – Affecting Gene Expression, Aging and Cancer – Onco’Zine – The International Cancer Network [Article]

Illustration Courtesy:  Parisha Shah, PhD; Shelley Berger, PhD, Perelman School of Medicine, University of Pennsylvania; Genes & Development

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