Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging

Genes and Development - Tập 28 Số 4 - Trang 396-408 - 2014
Wang Jian-hu1, Kaifu Chen2,3, Zheng Xia2,3, Myrriah Chavez-Tomar1,4, Sangita Pal1,5, Ja-Hwan Seol1, Chih‐Cheng Chen1, Wei Li2, Jessica K. Tyler1
11Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA
22Dan L. Duncan Cancer Center,
33Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
44Molecular Biology Graduate Program, University of Colorado School of Medicine, Denver, Colorado 80010, USA
55Genes and Development Graduate Program, The University of Texas Graduate School of Biomedical Sciences, Houston, Texas 77030, USA

Tóm tắt

All eukaryotic cells divide a finite number of times, although the mechanistic basis of this replicative aging remains unclear. Replicative aging is accompanied by a reduction in histone protein levels, and this is a cause of aging in budding yeast. Here we show that nucleosome occupancy decreased by 50% across the whole genome during replicative aging using spike-in controlled micrococcal nuclease digestion followed by sequencing. Furthermore, nucleosomes became less well positioned or moved to sequences predicted to better accommodate histone octamers. The loss of histones during aging led to transcriptional induction of all yeast genes. Genes that are normally repressed by promoter nucleosomes were most induced, accompanied by preferential nucleosome loss from their promoters. We also found elevated levels of DNA strand breaks, mitochondrial DNA transfer to the nuclear genome, large-scale chromosomal alterations, translocations, and retrotransposition during aging.

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Tài liệu tham khảo

10.1016/j.molcel.2005.12.010

10.1016/S0092-8674(04)00205-3

10.1038/nrg3017

10.1016/0092-8674(85)90197-7

10.1093/nar/gkn626

10.1016/S1672-0229(10)60010-1

10.1101/gr.141952.112

10.1101/gr.142067.112

10.1111/acel.12047

10.1016/j.molcel.2010.08.015

10.1016/j.molcel.2009.06.023

10.1371/journal.pgen.1002771

10.1016/0092-8674(88)90258-9

10.1083/jcb.201212110

10.1038/nature07667

10.1083/jcb.127.6.1985

1998, Transposable elements and genome organization: A comprehensive survey of retrotransposons revealed by the complete Saccharomyces cerevisiae genome sequence, Genome Res, 8, 464, 10.1101/gr.8.5.464

10.1002/bies.20723

10.1073/pnas.0307929101

10.1038/ng2117

10.1091/mbc.E03-10-0742

10.1074/jbc.M103509200

10.1534/genetics.109.106229

10.1371/journal.pgen.1002015

10.1016/j.cmet.2012.06.002

10.1016/j.cell.2012.10.012

10.1101/gr.078261.108

10.1126/science.1090701

10.1038/nsmb.1897

10.1038/47076

10.1093/nar/gkr557

10.1016/S0092-8674(00)80493-6

10.1016/S0092-8674(00)81038-7

10.1007/s004380000285

1993, Nuclear mutations in Saccharomyces cerevisiae that affect the escape of DNA from mitochondria to the nucleus, Genetics, 134, 21, 10.1093/genetics/134.1.21

10.1016/j.molcel.2011.01.015

10.4161/cc.10.17.17543

10.1093/gerona/63.1.21

10.1128/MCB.01733-07

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Genes and Development

Tập 28 Số 4

396-408

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