Dynamic Chromatin Localization of Sirt6 Shapes Stress- and Aging-Related Transcriptional Networks

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The sirtuin Sirt6 is a NAD-dependent histone deacetylase that is implicated in gene regulation and lifespan control. Sirt6 can interact with the stress-responsive transcription factor NF-κB and regulate some NF-κB target genes, but the full scope of Sirt6 target genes as well as dynamics of Sirt6 occupancy on chromatin are not known. Here we map Sirt6 occupancy on mouse promoters genome-wide and show that Sirt6 occupancy is highly dynamic in response to TNF-α. More than half of Sirt6 target genes are only revealed upon stress-signaling. The majority of genes bound by NF-κB subunit RelA recruit Sirt6, and dynamic Sirt6 relocalization is largely driven in a RelA-dependent manner. Integrative analysis with global gene expression patterns in wild-type, Sirt6−/−, and double Sirt6−/− RelA−/− cells reveals the epistatic relationships between Sirt6 and RelA in shaping diverse temporal patterns of gene expression. Genes under the direct joint control of Sirt6 and RelA include several with prominent roles in cell senescence and organismal aging. These data suggest dynamic chromatin relocalization of Sirt6 as a key output of NF-κB signaling in stress response and aging.

Vyšlo v časopise: Dynamic Chromatin Localization of Sirt6 Shapes Stress- and Aging-Related Transcriptional Networks. PLoS Genet 7(6): e32767. doi:10.1371/journal.pgen.1002153
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002153

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Zdroje

1. ImaiSArmstrongCMKaeberleinMGuarenteL 2000 Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403 795 800

2. LandryJSuttonATafrovSTHellerRCStebbinsJ 2000 The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. Proc Natl Acad Sci U S A 97 5807 5811

3. SmithJSBrachmannCBCelicIKennaMAMuhammadS 2000 A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family. Proc Natl Acad Sci U S A 97 6658 6663

4. XuFZhangQZhangKXieWGrunsteinM 2007 Sir2 deacetylates histone H3 lysine 56 to regulate telomeric heterochromatin structure in yeast. Mol Cell 27 890 900

5. DenuJM 2003 Linking chromatin function with metabolic networks: Sir2 family of NAD(+)-dependent deacetylases. Trends Biochem Sci 28 41 48

6. FryeRA 1999 Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. Biochem Biophys Res Commun 260 273 279

7. FryeRA 2000 Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun 273 793 798

8. McCordRAMichishitaEHongTBerberEBoxerLD 2009 SIRT6 stabilizes DNA-dependent protein kinase at chromatin for DNA double-strand break repair. Aging (Albany NY) 1 109 121

9. MichishitaEMcCordRABerberEKioiMPadilla-NashH 2008 SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452 492 496

10. KawaharaTLMichishitaEAdlerASDamianMBerberE 2009 SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span. Cell 136 62 74

11. MostoslavskyRChuaKFLombardDBPangWWFischerMR 2006 Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124 315 329

12. ZhongLDUrsoAToiberDSebastianCHenryRE The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell 140 280 293

13. TennenRIChuaKF Chromatin regulation and genome maintenance by mammalian SIRT6. Trends Biochem Sci 36 39 46

14. HaydenMSGhoshS 2008 Shared principles in NF-kappaB signaling. Cell 132 344 362

15. HaydenMSGhoshS 2004 Signaling to NF-kappaB. Genes Dev 18 2195 2224

16. GhoshSMayMJKoppEB 1998 NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol 16 225 260

17. HoffmannABaltimoreD 2006 Circuitry of nuclear factor kappaB signaling. Immunol Rev 210 171 186

18. FosterSLHargreavesDCMedzhitovR 2007 Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 447 972 978

19. AdlerASSinhaSKawaharaTLZhangJYSegalE 2007 Motif module map reveals enforcement of aging by continual NF-kappaB activity. Genes Dev 21 3244 3257

20. WangZZangCCuiKSchonesDEBarskiA 2009 Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes. Cell 138 1019 1031

21. GazinCWajapeyeeNGobeilSVirbasiusCMGreenMR 2007 An elaborate pathway required for Ras-mediated epigenetic silencing. Nature 449 1073 1077

22. HoffmannALevchenkoAScottMLBaltimoreD 2002 The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation. Science 298 1241 1245

23. CovertMWLeungTHGastonJEBaltimoreD 2005 Achieving stability of lipopolysaccharide-induced NF-kappaB activation. Science 309 1854 1857

24. TaySHugheyJJLeeTKLipniackiTQuakeSR Single-cell NF-kappaB dynamics reveal digital activation and analogue information processing. Nature 466 267 271

25. SchreiberJJennerRGMurrayHLGerberGKGiffordDK 2006 Coordinated binding of NF-kappaB family members in the response of human cells to lipopolysaccharide. Proc Natl Acad Sci U S A 103 5899 5904

26. LimCAYaoFWongJJGeorgeJXuH 2007 Genome-wide mapping of RELA(p65) binding identifies E2F1 as a transcriptional activator recruited by NF-kappaB upon TLR4 activation. Mol Cell 27 622 635

27. MigliaccioEGiorgioMMeleSPelicciGReboldiP 1999 The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402 309 313

28. KrishnamurthyJTorriceCRamseyMRKovalevGIAl-RegaieyK 2004 Ink4a/Arf expression is a biomarker of aging. J Clin Invest 114 1299 1307

29. JanzenVForkertRFlemingHESaitoYWaringMT 2006 Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443 421 426

30. BrackASConboyMJRoySLeeMKuoCJ 2007 Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science 317 807 810

31. LiuHFergussonMMCastilhoRMLiuJCaoL 2007 Augmented Wnt signaling in a mammalian model of accelerated aging. Science 317 803 806

32. De SmaeleEZazzeroniFPapaSNguyenDUJinR 2001 Induction of gadd45beta by NF-kappaB downregulates pro-apoptotic JNK signalling. Nature 414 308 313

33. MendrysaSMMcElweeMKPerryME 2001 Characterization of the 5′ and 3′ untranslated regions in murine mdm2 mRNAs. Gene 264 139 146

34. MounkesLCKozlovSHernandezLSullivanTStewartCL 2003 A progeroid syndrome in mice is caused by defects in A-type lamins. Nature 423 298 301

35. WuARHiattJBLuRAttemaJLLoboNA 2009 Automated microfluidic chromatin immunoprecipitation from 2,000 cells. Lab Chip 9 1365 1370

36. ErikssonMBrownWTGordonLBGlynnMWSingerJ 2003 Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423 293 298

37. SouthworthLKOwenABKimSK 2009 Aging mice show a decreasing correlation of gene expression within genetic modules. PLoS Genet 5 e1000776 doi:10.1371/journal.pgen.1000776

38. AdlerASKawaharaTLSegalEChangHY 2008 Reversal of aging by NFkappaB blockade. Cell Cycle 7 556 559

39. MartinSGLarocheTSukaNGrunsteinMGasserSM 1999 Relocalization of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast. Cell 97 621 633

40. OberdoerfferPMichanSMcVayMMostoslavskyRVannJ 2008 SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell 135 907 918

41. PerkinsND 2007 Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 8 49 62

42. KasowskiMGrubertFHeffelfingerCHariharanMAsabereA Variation in transcription factor binding among humans. Science 328 232 235

43. DahlJACollasP 2008 A rapid micro chromatin immunoprecipitation assay (microChIP). Nat Protoc 3 1032 1045

44. EisenMBSpellmanPTBrownPOBotsteinD 1998 Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A 95 14863 14868