Trimethylation of Lys36 on H3 restricts gene expression change during aging and impacts life span

Genes and Development - Tập 29 Số 7 - Trang 718-731 - 2015
Mintie Pu1, Zhuoyu Ni1, Minghui Wang2, Xiujuan Wang1,3, Jason G. Wood4, Stephen L. Helfand4, Haiyuan Yu3, Siu Sylvia Lee1
11Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850, USA
22Computational Biology Service Unit, Cornell University, Ithaca, New York 14850, USA
33Department of Biostatistics and Computational Biology, Weill Institute, Cornell University, Ithaca, New York 14850, USA
44Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island 02912, USA

Tóm tắt

Functional data indicate that specific histone modification enzymes can be key to longevity inCaenorhabditis elegans, but the molecular basis of how chromatin structure modulates longevity is not well understood. In this study, we profiled the genome-wide pattern of trimethylation of Lys36 on histone 3 (H3K36me3) in the somatic cells of young and oldCaenorhabditis elegans.We revealed a new role of H3K36me3 in maintaining gene expression stability through aging with important consequences on longevity. We found that genes with dramatic expression change during aging are marked with low or even undetectable levels of H3K36me3 in their gene bodies irrespective of their corresponding mRNA abundance. Interestingly, 3′ untranslated region (UTR) length strongly correlates with H3K36me3 levels and age-dependent mRNA expression stability. A similar negative correlation between H3K36me3 marking and mRNA expression change during aging was also observed inDrosophila melanogaster, suggesting a conserved mechanism for H3K36me3 in suppressing age-dependent mRNA expression change. Importantly, inactivation of the methyltransferasemet-1resulted in a decrease in global H3K36me3 marks, an increase in mRNA expression change with age, and a shortened life span, suggesting a causative role of the H3K36me3 marking in modulating age-dependent gene expression stability and longevity.

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Tài liệu tham khảo

10.1242/dev.009373

10.1016/j.cell.2007.05.009

10.1051/medsci/20031967725

10.1016/j.cell.2008.05.044

10.1016/j.cell.2005.10.023

10.1101/gr.153668.112

10.1371/journal.pgen.0030056

10.1038/nature08085

10.1038/nsmb.2123

10.1093/bioinformatics/btp073

10.1038/sj.emboj.7601967

10.1038/ng1983

10.1016/j.febslet.2010.11.016

10.1016/j.cell.2010.09.009

10.1007/s00401-013-1095-8

10.1186/gb-2013-14-7-r75

Golden TR , Melov S . 2007. Gene expression changes associated with aging in C. elegans . WormBook 1–12.

10.1038/nature09195

10.1038/nature10572

10.1101/gad.1308205

10.1016/S0092-8674(03)00360-X

10.1016/j.molcel.2012.10.016

10.1016/j.molcel.2010.05.004

10.1371/journal.pone.0003024

10.1186/gb-2013-14-10-r115

10.1038/nprot.2008.211

10.1016/j.cmet.2011.07.001

10.2174/138920212803251436

10.1016/S1046-2023(03)00050-1

10.1073/pnas.081061898

10.1038/nbt.1508

10.1091/mbc.10.10.3125

10.1073/pnas.1109475108

10.1038/ng.322

10.1016/j.cell.2007.02.005

10.7554/eLife.00808

2014, Proteostasis and longevity: when does aging really begin?, F1000prime Rep, 6, 7

10.1101/gr.136184.111

10.1186/gb-2009-10-3-r25

10.1126/science.285.5432.1390

10.1038/77046

10.1093/bioinformatics/btp324

10.1101/gad.1539307

10.1093/bioinformatics/btp352

10.1016/j.cell.2013.03.025

10.1186/gb-2011-12-8-r83

10.1126/science.1191244

10.1111/j.1474-9726.2011.00738.x

10.1038/ng1291

10.1074/jbc.M705028200

10.1038/nature06008

10.1016/S0960-9822(02)00808-4

10.1016/j.cell.2005.06.026

10.1371/journal.pgen.1002717

10.1016/0092-8674(87)90129-2

10.1186/1471-2164-15-284

10.1146/annurev.biochem.75.103004.142422

10.1073/pnas.0907739107

10.1101/gr.158253.113

10.1242/jcs.099200

10.1038/nsmb.2312

10.1101/gr.114595.110

10.1093/bioinformatics/btp120

10.1038/nbt.1621

10.1038/nprot.2012.016

10.1038/nature11326

10.1038/nrm3274

10.1038/nature13045

10.1186/gb4033

2013, Chromatin structure and transposable elements in organismal aging, Front Genet, 4, 274

10.1111/j.1474-9726.2010.00624.x

10.1186/1471-2164-13-S7-S14

10.1371/journal.pgen.1002082

10.1371/journal.pgen.0020115

10.1073/pnas.260496697

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Genes and Development

Tập 29 Số 7

718-731

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