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The Sir4 C-terminal coiled coil is required for telomeric and mating type silencing in Saccharomyces cerevisiae.

Murphy GA, Spedale EJ, Powell ST, Pillus L, Schultz SC, Chen L
J Mol Biol 334 769-80 (2003)
Cited: 25 times
EuropePMC logo PMID: 14636601

Abstract

Saccharomyces cerevisiae Sir4p plays important roles in silent chromatin at telomeric and silent mating type loci. The C terminus of Sir4p (Sir4CT) is critical for its functions in vivo because over-expression or deletion of Sir4CT fragments disrupts normal telomeric structure and abolishes the telomere position effect. The 2.5A resolution X-ray crystal structure of an Sir4CT fragment (Sir4p 1217-1358) reveals a 72 residue homodimeric, parallel coiled coil, burying an extensive 3600A(2) of surface area. The crystal structure is consistent with results of protein cross-linking and analytical ultracentrifugation results demonstrating that Sir4CT exists as a dimer in solution. Disruption of the coiled coil in vivo by point mutagenesis results in total derepression of telomeric and HML silent mating marker genes, suggesting that coiled coil dimerization is essential for Sir4p-mediated silencing. In addition to the coiled coil dimerization interface (Sir4CC interface), a crystallographic interface between pairs of coiled coils is significantly hydrophobic and buries 1228A(2) of surface area (interface II). Remarkably, interface II mutants are deficient in telomeric silencing but not in mating type silencing in vivo. However, point mutants of interface II do not affect the oligomerization state of Sir4CT in solution. These results are consistent with the hypothesis that interface II mimics a protein interface between Sir4p and one of its protein partners that is essential for telomeric silencing but not mating type silencing.

Articles - 1pl5 mentioned but not cited (3)

  1. Structural attributes for the recognition of weak and anomalous regions in coiled-coils of myosins and other motor proteins. Sunitha MS, Nair AG, Charya A, Jadhav K, Mukhopadhyay S, Sowdhamini R. BMC Res Notes 5 530 (2012)
  2. Discovery and Evolution of New Domains in Yeast Heterochromatin Factor Sir4 and Its Partner Esc1. Faure G, Jézéquel K, Roisné-Hamelin F, Bitard-Feildel T, Lamiable A, Marcand S, Callebaut I. Genome Biol Evol 11 572-585 (2019)
  3. Variants of the Sir4 Coiled-Coil Domain Improve Binding to Sir3 for Heterochromatin Formation in Saccharomyces cerevisiae. Samel A, Rudner A, Ehrenhofer-Murray AE. G3 (Bethesda) 7 1117-1126 (2017)


Reviews citing this publication (7)

  1. The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae. Gartenberg MR, Smith JS. Genetics 203 1563-1599 (2016)
  2. SIR proteins and the assembly of silent chromatin in budding yeast. Kueng S, Oppikofer M, Gasser SM. Annu Rev Genet 47 275-306 (2013)
  3. Epigenetics in Saccharomyces cerevisiae. Grunstein M, Gasser SM. Cold Spring Harb Perspect Biol 5 a017491 (2013)
  4. Reinventing heterochromatin in budding yeasts: Sir2 and the origin recognition complex take center stage. Hickman MA, Froyd CA, Rusche LN. Eukaryot Cell 10 1183-1192 (2011)
  5. Building silent compartments at the nuclear periphery: a recurrent theme. Meister P, Taddei A. Curr Opin Genet Dev 23 96-103 (2013)
  6. SIR-nucleosome interactions: structure-function relationships in yeast silent chromatin. Oppikofer M, Kueng S, Gasser SM. Gene 527 10-25 (2013)
  7. The regional sequestration of heterochromatin structural proteins is critical to form and maintain silent chromatin. Oh J, Yeom S, Park J, Lee JS. Epigenetics Chromatin 15 5 (2022)

Articles citing this publication (15)

  1. Comparative genomics in hemiascomycete yeasts: evolution of sex, silencing, and subtelomeres. Fabre E, Muller H, Therizols P, Lafontaine I, Dujon B, Fairhead C. Mol Biol Evol 22 856-873 (2005)
  2. Reconstitution of yeast silent chromatin: multiple contact sites and O-AADPR binding load SIR complexes onto nucleosomes in vitro. Martino F, Kueng S, Robinson P, Tsai-Pflugfelder M, van Leeuwen F, Ziegler M, Cubizolles F, Cockell MM, Rhodes D, Gasser SM. Mol Cell 33 323-334 (2009)
  3. Dot1 and histone H3K79 methylation in natural telomeric and HM silencing. Takahashi YH, Schulze JM, Jackson J, Hentrich T, Seidel C, Jaspersen SL, Kobor MS, Shilatifard A. Mol Cell 42 118-126 (2011)
  4. A nonhistone protein-protein interaction required for assembly of the SIR complex and silent chromatin. Rudner AD, Hall BE, Ellenberger T, Moazed D. Mol Cell Biol 25 4514-4528 (2005)
  5. Crystal structure of a conserved N-terminal domain of histone deacetylase 4 reveals functional insights into glutamine-rich domains. Guo L, Han A, Bates DL, Cao J, Chen L. Proc Natl Acad Sci U S A 104 4297-4302 (2007)
  6. Domain structure and protein interactions of the silent information regulator Sir3 revealed by screening a nested deletion library of protein fragments. King DA, Hall BE, Iwamoto MA, Win KZ, Chang JF, Ellenberger T. J Biol Chem 281 20107-20119 (2006)
  7. Dimerization of Sir3 via its C-terminal winged helix domain is essential for yeast heterochromatin formation. Oppikofer M, Kueng S, Keusch JJ, Hassler M, Ladurner AG, Gut H, Gasser SM. EMBO J 32 437-449 (2013)
  8. Heterochromatin assembly by interrupted Sir3 bridges across neighboring nucleosomes. Behrouzi R, Lu C, Currie MA, Jih G, Iglesias N, Moazed D. Elife 5 e17556 (2016)
  9. Regulating repression: roles for the sir4 N-terminus in linker DNA protection and stabilization of epigenetic states. Kueng S, Tsai-Pflugfelder M, Oppikofer M, Ferreira HC, Roberts E, Tsai C, Roloff TC, Sack R, Gasser SM. PLoS Genet 8 e1002727 (2012)
  10. Conformational Dynamics of Asparagine at Coiled-Coil Interfaces. Thomas F, Niitsu A, Oregioni A, Bartlett GJ, Woolfson DN. Biochemistry 56 6544-6554 (2017)
  11. Retrotransposon target site selection by imitation of a cellular protein. Brady TL, Fuerst PG, Dick RA, Schmidt C, Voytas DF. Mol Cell Biol 28 1230-1239 (2008)
  12. SIR proteins create compact heterochromatin fibers. Swygert SG, Senapati S, Bolukbasi MF, Wolfe SA, Lindsay S, Peterson CL. Proc Natl Acad Sci U S A 115 12447-12452 (2018)
  13. The Sir4 H-BRCT domain interacts with phospho-proteins to sequester and repress yeast heterochromatin. Deshpande I, Keusch JJ, Challa K, Iesmantavicius V, Gasser SM, Gut H. EMBO J 38 e101744 (2019)
  14. Expression profile of mouse Mterfd2, a novel component of the mitochondrial transcription termination factor (MTERF) family. Xu Q, Zhang F, He H, Xu S, Li K, Liu S, Li Y, Wu Q. Genes Genet Syst 86 269-275 (2011)
  15. Clinical significance of aberrant DEUP1 promoter methylation in hepatocellular carcinoma. Yu Q, Cao S, Tang H, Li J, Guo W, Zhang S. Oncol Lett 18 1356-1364 (2019)


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