Heterochromatin assembly by interrupted Sir3 bridges across neighboring nucleosomes
- PMID: 27835568
- PMCID: PMC5106214
- DOI: 10.7554/eLife.17556
Heterochromatin assembly by interrupted Sir3 bridges across neighboring nucleosomes
Abstract
Heterochromatin is a conserved feature of eukaryotic chromosomes with central roles in regulation of gene expression and maintenance of genome stability. Heterochromatin formation involves spreading of chromatin-modifying factors away from initiation points over large DNA domains by poorly understood mechanisms. In Saccharomyces cerevisiae, heterochromatin formation requires the SIR complex, which contains subunits with histone-modifying, histone-binding, and self-association activities. Here, we analyze binding of the Sir proteins to reconstituted mono-, di-, tri-, and tetra-nucleosomal chromatin templates and show that key Sir-Sir interactions bridge only sites on different nucleosomes but not sites on the same nucleosome, and are therefore 'interrupted' with respect to sites on the same nucleosome. We observe maximal binding affinity and cooperativity to unmodified di-nucleosomes and propose that nucleosome pairs bearing unmodified histone H4-lysine16 and H3-lysine79 form the fundamental units of Sir chromatin binding and that cooperative binding requiring two appropriately modified nucleosomes mediates selective Sir recruitment and spreading.
Keywords: S. cerevisiae; Sir3; Sir4; biochemistry; chromatin spreading; chromosomes; genes; heterochromatin; nucleosome.
Conflict of interest statement
The authors declare that no competing interests exist.
Figures
















Similar articles
-
Stabilization of Sir3 interactions by an epigenetic metabolic small molecule, O-acetyl-ADP-ribose, on yeast SIR-nucleosome silent heterochromatin.Arch Biochem Biophys. 2019 Aug 15;671:167-174. doi: 10.1016/j.abb.2019.07.005. Epub 2019 Jul 8. Arch Biochem Biophys. 2019. PMID: 31295433
-
Sir3-nucleosome interactions in spreading of silent chromatin in Saccharomyces cerevisiae.Mol Cell Biol. 2008 Nov;28(22):6903-18. doi: 10.1128/MCB.01210-08. Epub 2008 Sep 15. Mol Cell Biol. 2008. PMID: 18794362 Free PMC article.
-
SIR proteins create compact heterochromatin fibers.Proc Natl Acad Sci U S A. 2018 Dec 4;115(49):12447-12452. doi: 10.1073/pnas.1810647115. Epub 2018 Nov 19. Proc Natl Acad Sci U S A. 2018. PMID: 30455303 Free PMC article.
-
A model for step-wise assembly of heterochromatin in yeast.Novartis Found Symp. 2004;259:48-56; discussion 56-62, 163-9. Novartis Found Symp. 2004. PMID: 15171246 Review.
-
SIR proteins and the assembly of silent chromatin in budding yeast.Annu Rev Genet. 2013;47:275-306. doi: 10.1146/annurev-genet-021313-173730. Epub 2013 Sep 4. Annu Rev Genet. 2013. PMID: 24016189 Review.
Cited by
-
Distinct structural groups of histone H3 and H4 residues have divergent effects on chronological lifespan in Saccharomyces cerevisiae.PLoS One. 2022 May 27;17(5):e0268760. doi: 10.1371/journal.pone.0268760. eCollection 2022. PLoS One. 2022. PMID: 35622816 Free PMC article.
-
Evolution of DNA replication origin specification and gene silencing mechanisms.Nat Commun. 2020 Oct 14;11(1):5175. doi: 10.1038/s41467-020-18964-x. Nat Commun. 2020. PMID: 33056978 Free PMC article.
-
Recruitment and allosteric stimulation of a histone-deubiquitinating enzyme during heterochromatin assembly.J Biol Chem. 2018 Feb 16;293(7):2498-2509. doi: 10.1074/jbc.RA117.000498. Epub 2017 Dec 29. J Biol Chem. 2018. PMID: 29288197 Free PMC article.
-
Nucleosome Positioning Regulates the Establishment, Stability, and Inheritance of Heterochromatin in Saccharomyces cerevisiae.Proc Natl Acad Sci U S A. 2020 Nov 3;117(44):27493-27501. doi: 10.1073/pnas.2004111117. Epub 2020 Oct 19. Proc Natl Acad Sci U S A. 2020. PMID: 33077593 Free PMC article.
-
Prevalent and dynamic binding of the cell cycle checkpoint kinase Rad53 to gene promoters.Elife. 2022 Dec 15;11:e84320. doi: 10.7554/eLife.84320. Elife. 2022. PMID: 36520028 Free PMC article.
References
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases