SIR4/YDR227W Summary Help

Standard Name SIR4 1
Systematic Name YDR227W
Alias ASD1 , STE9 , UTH2
Feature Type ORF, Verified
Description SIR protein involved in assembly of silent chromatin domains; silent information regulator (SIR) along with SIR2 and SIR3; involved in assembly of silent chromatin domains at telomeres and the silent mating-type loci; potentially phosphorylated by Cdc28p; some alleles of SIR4 prolong lifespan (2, 3, 4 and see Summary Paragraph)
Name Description Silent Information Regulator 1
Chromosomal Location
ChrIV:917571 to 921647 | ORF Map | GBrowse
Genetic position: 128 cM
Gene Ontology Annotations All SIR4 GO evidence and references
  View Computational GO annotations for SIR4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 3 genes
Classical genetics
gain of function
Large-scale survey
229 total interaction(s) for 94 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 22
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 44
  • Biochemical Activity: 4
  • Co-crystal Structure: 2
  • Co-localization: 5
  • Co-purification: 5
  • PCA: 1
  • Reconstituted Complex: 23
  • Two-hybrid: 61

Genetic Interactions
  • Dosage Rescue: 9
  • Phenotypic Enhancement: 9
  • Phenotypic Suppression: 10
  • Synthetic Growth Defect: 12
  • Synthetic Rescue: 20

Expression Summary
Length (a.a.) 1,358
Molecular Weight (Da) 152,060
Isoelectric Point (pI) 9.77
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrIV:917571 to 921647 | ORF Map | GBrowse
Genetic position: 128 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..4077 917571..921647 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 SGDIDS000002635

SIR4 is one of four Silent Information Regulator genes in budding yeast (1). Sir4p participates in silencing the cryptic mating type loci HML and HMR, and helps maintain a repressed chromatin structure near telomeres (5). 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 (6, 7). The Sir proteins do not bind DNA directly, but rather seem to act via histones and other DNA binding proteins (6, 8, 9). 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 (10, 11, 12). Sir4p seems to act in the maintenance rather than the initiation of silencing at HML and HMR (13). Genetic and physical interactions between Sir2p and Sir4p, Sir3p and Sir4p, and Rap1p and Sir4p have been detected (14, 15, 16, 17, 3, 18, 19, 20). These four proteins act together at telomeres to create a repressed heterochromatin structure (5, 19, 14). Sir4p has also been shown to interact with histones H3 and H4, consistent with its role in shaping the architecture of the chromatin at HML, HMR, and telomeres (21).

Sir4p seems to play a role in the aging of yeast cells. An allele of SIR4 was found that extends the life span of yeast (2). In strains with this SIR4 allele, Sir3p and Sir4p are redirected to the nucleolus rather than telomeres (22). Mutations in SIR4 that lead to a longer life span also result in enhanced rDNA silencing (23, 24). It may be that the lengthening of life span is due to the prevention of formation of extrachromosomal rDNA circles (ercs) that form through homologous recombination within rDNA arrays, which is inhibited when the rDNA is silenced (25).

A functional homolog of Sir4p exists in Kluveromyces lactis (26).

Last updated: 1999-09-01 Contact SGD

References cited on this page View Complete Literature Guide for SIR4
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) Kennedy BK, et al.  (1995) Mutation in the silencing gene SIR4 can delay aging in S. cerevisiae. Cell 80(3):485-96
3) 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
4) Ubersax JA, et al.  (2003) Targets of the cyclin-dependent kinase Cdk1. Nature 425(6960):859-64
5) 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
6) Laurenson P and Rine J  (1992) Silencers, silencing, and heritable transcriptional states. Microbiol Rev 56(4):543-60
7) Loo S and Rine J  (1994) Silencers and domains of generalized repression. Science 264(5166):1768-71
8) Shore D  (1994) RAP1: a protean regulator in yeast. Trends Genet 10(11):408-12
9) Loo S and Rine J  (1995) Silencing and heritable domains of gene expression. Annu Rev Cell Dev Biol 11:519-48
10) 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
11) 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
12) Triolo T and Sternglanz R  (1996) Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing. Nature 381(6579):251-3
13) Pillus L and Rine J  (1989) Epigenetic inheritance of transcriptional states in S. cerevisiae. Cell 59(4):637-47
14) 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
15) 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
16) Ivy JM, et al.  (1986) Cloning and characterization of four SIR genes of Saccharomyces cerevisiae. Mol Cell Biol 6(2):688-702
17) 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
18) Palladino F, et al.  (1993) SIR3 and SIR4 proteins are required for the positioning and integrity of yeast telomeres. Cell 75(3):543-55
19) 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
20) Sussel L and Shore D  (1991) Separation of transcriptional activation and silencing functions of the RAP1-encoded repressor/activator protein 1: isolation of viable mutants affecting both silencing and telomere length. Proc Natl Acad Sci U S A 88(17):7749-53
21) 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
22) 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
23) Smith JS and Boeke JD  (1997) An unusual form of transcriptional silencing in yeast ribosomal DNA. Genes Dev 11(2):241-54
24) Smith JS, et al.  (1998) Distribution of a limited Sir2 protein pool regulates the strength of yeast rDNA silencing and is modulated by Sir4p. Genetics 149(3):1205-19
25) 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
26) Astrom SU and Rine J  (1998) Theme and variation among silencing proteins in Saccharomyces cerevisiae and Kluyveromyces lactis. Genetics 148(3):1021-9