Home LiteratureArticle Details
PMID: 16581798 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Structure and function of the Saccharomyces cerevisiae Sir3 BAH domain.

Molecular and cellular biology ·Vol. 26 ·No. 8 ·2006-04-00 ·Pages 3256-65

Connelly JJ, Yuan P, Hsu HC, Li Z, Xu RM, Sternglanz R

Abstract

Previous work has shown that the N terminus of the Saccharomyces cerevisiae Sir3 protein is crucial for the function of Sir3 in transcriptional silencing. Here, we show that overexpression of N-terminal fragments of Sir3 in strains lacking the full-length protein can lead to some silencing of HML and HMR. Sir3 contains a BAH (bromo-adjacent homology) domain at its N terminus. Overexpression of this domain alone can lead to silencing as long as Sir1 is overexpressed and Sir2 and Sir4 are present. Overexpression of the closely related Orc1 BAH domain can also silence in the absence of any Sir3 protein. A previously characterized hypermorphic sir3 mutation, D205N, greatly improves silencing by the Sir3 BAH domain and allows it to bind to DNA and oligonucleosomes in vitro. A previously uncharacterized region in the Sir1 N terminus is required for silencing by both the Sir3 and Orc1 BAH domains. The structure of the Sir3 BAH domain has been determined. In the crystal, the molecule multimerizes in the form of a left-handed superhelix. This superhelix may be relevant to the function of the BAH domain of Sir3 in silencing.

MeSH Terms
Amino Acid Sequence Binding Sites Chromatin Immunoprecipitation Conserved Sequence Crystallography, X-Ray Dimerization Escherichia coli/genetics Gene Silencing Histidine/chemistry Models, Molecular Molecular Sequence Data Nucleosomes/metabolism Plasmids/metabolism Point Mutation Protein Binding Protein Structure, Tertiary Recombinant Fusion Proteins/chemistry,metabolism Saccharomyces cerevisiae/chemistry,genetics,metabolism Saccharomyces cerevisiae Proteins/chemistry,genetics,metabolism Silent Information Regulator Proteins, Saccharomyces cerevisiae/chemistry,genetics,metabolism Static Electricity
Chemicals
Nucleosomes Recombinant Fusion Proteins SIR3 protein, S cerevisiae Saccharomyces cerevisiae Proteins Silent Information Regulator Proteins, Saccharomyces cerevisiae Histidine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Connelly Jessica J
W. M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA .
Yuan Peihua
Hsu Hao-Chi
Li Zhizhong
Xu Rui-Ming
Sternglanz Rolf
References (39)
39 references, click to expand
  1. The BAH (bromo-adjacent homology) domain: a link between DNA methylation, replication and transcriptional regulation.
    FEBS Lett. 1999 Mar 5;446(1):189-93 PMID: 10100640
  2. Two classes of sir3 mutants enhance the sir1 mutant mating defect and abolish telomeric silencing in Saccharomyces cerevisiae.
    Genetics. 2000 Jun;155(2):509-22 PMID: 10835377
  3. Heterochromatin protein 1 binds to nucleosomes and DNA in vitro.
    J Biol Chem. 2000 Sep 8;275(36):28332-8 PMID: 10882726
  4. Silenced chromatin is permissive to activator binding and PIC recruitment.
    Cell. 2001 May 4;105(3):403-14 PMID: 11348596
  5. Sir3-dependent assembly of supramolecular chromatin structures in vitro.
    Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8584-9 PMID: 11447281
  6. Promoter-specific binding of Rap1 revealed by genome-wide maps of protein-DNA association.
    Nat Genet. 2001 Aug;28(4):327-34 PMID: 11455386
  7. Sir2p exists in two nucleosome-binding complexes with distinct deacetylase activities.
    EMBO J. 2001 Aug 15;20(16):4522-35 PMID: 11500379
  8. Implementation of molecular replacement in AMoRe.
    Acta Crystallogr D Biol Crystallogr. 2001 Oct;57(Pt 10):1367-72 PMID: 11567147
  9. Acetylation of the yeast histone H4 N terminus regulates its binding to heterochromatin protein SIR3.
    J Biol Chem. 2002 Feb 15;277(7):4778-81 PMID: 11714726
  10. The molecular biology of the SIR proteins.
    Gene. 2001 Nov 14;279(1):1-16 PMID: 11722841
  11. Structure and function of the BAH-containing domain of Orc1p in epigenetic silencing.
    EMBO J. 2002 Sep 2;21(17):4600-11 PMID: 12198162
  12. Identification of a functional domain within the essential core of histone H3 that is required for telomeric and HM silencing in Saccharomyces cerevisiae.
    Genetics. 2003 Jan;163(1):447-52 PMID: 12586729
  13. The establishment, inheritance, and function of silenced chromatin in Saccharomyces cerevisiae.
    Annu Rev Biochem. 2003;72:481-516 PMID: 12676793
  14. The origin recognition complex and Sir4 protein recruit Sir1p to yeast silent chromatin through independent interactions requiring a common Sir1p domain.
    Mol Cell Biol. 2004 Jan;24(2):774-86 PMID: 14701749
  15. Importance of the Sir3 N terminus and its acetylation for yeast transcriptional silencing.
    Genetics. 2004 Sep;168(1):547-51 PMID: 15454564
  16. Dependence of ORC silencing function on NatA-mediated Nalpha acetylation in Saccharomyces cerevisiae.
    Mol Cell Biol. 2004 Dec;24(23):10300-12 PMID: 15542839
  17. Toward biochemical understanding of a transcriptionally silenced chromosomal domain in Saccharomyces cerevisiae.
    J Biol Chem. 2005 Mar 11;280(10):8629-32 PMID: 15623501
  18. Mechanism of transcriptional silencing in yeast.
    Cell. 2005 Jan 14;120(1):37-48 PMID: 15652480
  19. Assembly of the SIR complex and its regulation by O-acetyl-ADP-ribose, a product of NAD-dependent histone deacetylation.
    Cell. 2005 May 20;121(4):515-527 PMID: 15907466
  20. Structural basis of the Sir1-origin recognition complex interaction in transcriptional silencing.
    Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8489-94 PMID: 15932939
  21. Structural basis for origin recognition complex 1 protein-silence information regulator 1 protein interaction in epigenetic silencing.
    Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8519-24 PMID: 15937111
  22. The SIR1 gene of Saccharomyces cerevisiae and its role as an extragenic suppressor of several mating-defective mutants.
    Mol Cell Biol. 1991 Apr;11(4):2253-62 PMID: 2005909
  23. Improved methods for building protein models in electron density maps and the location of errors in these models.
    Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9 PMID: 2025413
  24. 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. 1990 Aug;87(16):6286-90 PMID: 2201024
  25. Processing of X-ray diffraction data collected in oscillation mode.
    Methods Enzymol. 1997;276:307-26 PMID: 27754618
  26. Extremely conserved histone H4 N terminus is dispensable for growth but essential for repressing the silent mating loci in yeast.
    Cell. 1988 Oct 7;55(1):27-39 PMID: 3048701
  27. The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing.
    Cell. 1995 Nov 17;83(4):563-8 PMID: 7585959
  28. Yeast vectors for the controlled expression of heterologous proteins in different genetic backgrounds.
    Gene. 1995 Apr 14;156(1):119-22 PMID: 7737504
  29. Targeting of SIR1 protein establishes transcriptional silencing at HM loci and telomeres in yeast.
    Cell. 1993 Nov 5;75(3):531-41 PMID: 8221892
  30. Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing.
    Nature. 1996 May 16;381(6579):251-3 PMID: 8622770
  31. Repression domain of the yeast global repressor Tup1 interacts directly with histones H3 and H4.
    Genes Dev. 1996 May 15;10(10):1247-59 PMID: 8675011
  32. Genetic analysis of Rap1p/Sir3p interactions in telomeric and HML silencing in Saccharomyces cerevisiae.
    Genetics. 1996 May;143(1):81-93 PMID: 8722764
  33. Two new S-phase-specific genes from Saccharomyces cerevisiae.
    Yeast. 1997 Sep 15;13(11):1029-42 PMID: 9290207
  34. Crystal structure of the nucleosome core particle at 2.8 A resolution.
    Nature. 1997 Sep 18;389(6648):251-60 PMID: 9305837
  35. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae.
    Yeast. 1998 Jul;14(10):953-61 PMID: 9717241
  36. Functional characterization of the N terminus of Sir3p.
    Mol Cell Biol. 1998 Oct;18(10):6110-20 PMID: 9742128
  37. Crystallography & NMR system: A new software suite for macromolecular structure determination.
    Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21 PMID: 9757107
  38. Sir3p domains involved in the initiation of telomeric silencing in Saccharomyces cerevisiae.
    Genetics. 1998 Nov;150(3):977-86 PMID: 9799252
  39. A region of the Sir1 protein dedicated to recognition of a silencer and required for interaction with the Orc1 protein in saccharomyces cerevisiae.
    Genetics. 1999 Jan;151(1):31-44 PMID: 9872946
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.26.8.3256-3265.2006
Published
2006-04-00
Pages
3256-65
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1446965
Subset
IM
Grants
NIGMS NIH HHS · GM 63716 · United States
NIGMS NIH HHS · R56 GM028220 · United States
NIGMS NIH HHS · R01 GM063716 · United States
NIGMS NIH HHS · R01 GM028220 · United States
NIGMS NIH HHS · GM 28220 · United States
Databases
PDB
2FYU
External Links
PubMed source DOI: 10.1128/MCB.26.8.3256-3265.2006 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2