SIR3/YLR442C Summary Help

Standard Name SIR3 1
Systematic Name YLR442C
Alias CMT1 2 , MAR2 3 , 4 , STE8 5
Feature Type ORF, Verified
Description Silencing protein; interacts with Sir2p, Sir4p, and histone H3 and H4 tails to establish transcriptionally silent chromatin state; required for spreading of silenced chromatin; recruited to chromatin through interaction with Rap1p; C-terminus (residues 840-978) assumes variant winged helix-turn-helix (wH) fold that mediates homodimerization, which is critical for holo-SIR complex loading; SIR3 has a paralog, ORC1, that arose from the whole genome duplication (1, 6, 7, 8, 9 and see Summary Paragraph)
Name Description Silent Information Regulator 1
Chromosomal Location
ChrXII:1022251 to 1019315 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: 337 cM
Gene Ontology Annotations All SIR3 GO evidence and references
  View Computational GO annotations for SIR3
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 1 genes
Classical genetics
Large-scale survey
256 total interaction(s) for 91 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 30
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 49
  • Biochemical Activity: 4
  • Co-crystal Structure: 2
  • Co-fractionation: 1
  • Co-localization: 10
  • Co-purification: 2
  • Protein-peptide: 4
  • Reconstituted Complex: 39
  • Two-hybrid: 25

Genetic Interactions
  • Dosage Lethality: 1
  • Dosage Rescue: 13
  • Phenotypic Enhancement: 10
  • Phenotypic Suppression: 13
  • Synthetic Growth Defect: 13
  • Synthetic Lethality: 1
  • Synthetic Rescue: 37

Expression Summary
Length (a.a.) 978
Molecular Weight (Da) 111,359
Isoelectric Point (pI) 6.29
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXII:1022251 to 1019315 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: 337 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..2937 1022251..1019315 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000004434

SIR3 is one of four Silent Information Regulator genes in budding yeast (1). Sir3p participates in silencing the cryptic mating type loci HML and HMR, and is a key player in maintaining a repressed chromatin structure near telomeres (10). Unlike repressors that act by binding to promoters, the Sir proteins help repress transcription by creating a silent chromatin stucture in a gene- and promoter-independent manner (11, 12). The Sir proteins do not bind DNA directly, but rather seem to act via histones and other DNA binding proteins (11, 13, 14). The exact means by which the Sir proteins create a silenced domain is unknown.

Silencing at HML and HMR depends on the presence of a regulatory chromosomal domain that binds multifunctional nuclear proteins such as Rap1p, Abf1p, and the Origin Recognition Complex (ORC); these proteins help recruit silencing-specific proteins Sir1p, Sir2p, Sir3p, and Sir4p (15, 16, 17). It appears that Rap1p recruits Sir3p to telomeres, where it acts along with Sir2p and Sir4p to maintain silencing (18, 19, 20, 6, 21, 22). The silenced domains located next to chromosome ends spread inward from the telomeres in proportion to Sir3p levels in the cell, and it appears that Sir3p is a structural component of the heterochromatin, as it is detected spreading inward along with the silenced domains (23, 6). In addition to documented interactions with Sir2p, Sir4p and Rap1p, Sir3p shows genetic and physical interactions with histones H3 and H4, consistent with its role in determining chromatin structure (24, 25, 26, 27, 28).

Sir3p also seems to play a role in the aging of yeast cells. The proportion of Sir3p found at telomeres versus the nucleolus decreases as cells age, and mutations in SGS1 or RAD52 which shorten the lifespan of yeast also result in the redistribution of Sir3p from telomeres to the nucleolus (29, 30, 31).

Last updated: 1999-09-01 Contact SGD

References cited on this page View Complete Literature Guide for SIR3
1) Rine J and Herskowitz I  (1987) Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae. Genetics 116(1):9-22
2) Hopper AK and Hall BD  (1975) Mutation of a heterothallic strain to homothallism. Genetics 80(1):77-85
3) Ivy JM, et al.  (1985) Map positions of yeast genes SIR1, SIR3 and SIR4. Genetics 111(4):735-44
4) Klar AJ, et al.  (1981) Regulation of transcription in expressed and unexpressed mating type cassettes of yeast. Nature 289(5795):239-44
5) Hartwell LH  (1980) Mutants of Saccharomyces cerevisiae unresponsive to cell division control by polypeptide mating hormone. J Cell Biol 85(3):811-22
6) Hecht A, et al.  (1996) Spreading of transcriptional repressor SIR3 from telomeric heterochromatin. Nature 383(6595):92-6
7) Moretti P and Shore D  (2001) Multiple interactions in Sir protein recruitment by Rap1p at silencers and telomeres in yeast. Mol Cell Biol 21(23):8082-94
8) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
9) Oppikofer M, et al.  (2013) Dimerization of Sir3 via its C-terminal winged helix domain is essential for yeast heterochromatin formation. EMBO J 32(3):437-49
10) Aparicio OM, et al.  (1991) Modifiers of position effect are shared between telomeric and silent mating-type loci in S. cerevisiae. Cell 66(6):1279-87
11) Laurenson P and Rine J  (1992) Silencers, silencing, and heritable transcriptional states. Microbiol Rev 56(4):543-60
12) Loo S and Rine J  (1994) Silencers and domains of generalized repression. Science 264(5166):1768-71
13) Shore D  (1994) RAP1: a protean regulator in yeast. Trends Genet 10(11):408-12
14) Loo S and Rine J  (1995) Silencing and heritable domains of gene expression. Annu Rev Cell Dev Biol 11:519-48
15) Kimmerly W, et al.  (1988) Roles of two DNA-binding factors in replication, segregation and transcriptional repression mediated by a yeast silencer. EMBO J 7(7):2241-53
16) Gardner KA, et al.  (1999) A region of the Sir1 protein dedicated to recognition of a silencer and required for interaction with the Orc1 protein in saccharomyces cerevisiae. Genetics 151(1):31-44
17) Triolo T and Sternglanz R  (1996) Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing. Nature 381(6579):251-3
18) Lustig AJ, et al.  (1996) Tethered Sir3p nucleates silencing at telomeres and internal loci in Saccharomyces cerevisiae. Mol Cell Biol 16(5):2483-95
19) Cockell M, et al.  (1995) The carboxy termini of Sir4 and Rap1 affect Sir3 localization: evidence for a multicomponent complex required for yeast telomeric silencing. J Cell Biol 129(4):909-24
20) Gotta M, et al.  (1996) The clustering of telomeres and colocalization with Rap1, Sir3, and Sir4 proteins in wild-type Saccharomyces cerevisiae. J Cell Biol 134(6):1349-63
21) Moretti P, et al.  (1994) Evidence that a complex of SIR proteins interacts with the silencer and telomere-binding protein RAP1. Genes Dev 8(19):2257-69
22) Marcand S, et al.  (1996) Silencing of genes at nontelomeric sites in yeast is controlled by sequestration of silencing factors at telomeres by Rap 1 protein. Genes Dev 10(11):1297-309
23) Renauld H, et al.  (1993) Silent domains are assembled continuously from the telomere and are defined by promoter distance and strength, and by SIR3 dosage. Genes Dev 7(7A):1133-45
24) Hecht A, et al.  (1995) Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for the formation of heterochromatin in yeast. Cell 80(4):583-92
25) Venditti S, et al.  (1999) Heterochromatin organization of a natural yeast telomere. Recruitment of Sir3p through interaction with histone H4 N terminus is required for the establishment of repressive structures. J Biol Chem 274(4):1928-33
26) Strahl-Bolsinger S, et al.  (1997) SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeast. Genes Dev 11(1):83-93
27) Moazed D, et al.  (1997) Silent information regulator protein complexes in Saccharomyces cerevisiae: a SIR2/SIR4 complex and evidence for a regulatory domain in SIR4 that inhibits its interaction with SIR3. Proc Natl Acad Sci U S A 94(6):2186-91
28) Johnson LM, et al.  (1990) Genetic evidence for an interaction between SIR3 and histone H4 in the repression of the silent mating loci in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 87(16):6286-90
29) Sinclair DA, et al.  (1997) Accelerated aging and nucleolar fragmentation in yeast sgs1 mutants. Science 277(5330):1313-6
30) Kennedy BK, et al.  (1997) Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae. Cell 89(3):381-91
31) Park PU, et al.  (1999) Effects of mutations in DNA repair genes on formation of ribosomal DNA circles and life span in Saccharomyces cerevisiae. Mol Cell Biol 19(5):3848-56