Home LiteratureArticle Details
PMID: 10958692 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Conservation of heterochromatin protein 1 function.

Molecular and cellular biology ·Vol. 20 ·No. 18 ·2000-09-00 ·Pages 6970-83

Wang G, Ma A, Chow CM, Horsley D, Brown NR, Cowell IG, Singh PB

Abstract

Heterochromatin represents a cytologically visible state of heritable gene repression. In the yeast, Schizosaccharomyces pombe, the swi6 gene encodes a heterochromatin protein 1 (HP1)-like chromodomain protein that localizes to heterochromatin domains, including the centromeres, telomeres, and the donor mating-type loci, and is involved in silencing at these loci. We identify here the functional domains of swi6p and demonstrate that the chromodomain from a mammalian HP1-like protein, M31, can functionally replace that of swi6p, showing that chromodomain function is conserved from yeasts to humans. Site-directed mutagenesis, based on a modeled three-dimensional structure of the swi6p chromodomain, shows that the hydrophobic amino acids which lie in the core of the structure are critical for biological function. Gel filtration, gel overlay experiments, and mass spectroscopy show that HP1 proteins can self-associate, and we suggest that it is as oligomers that HP1 proteins are incorporated into heterochromatin complexes that silence gene activity.

MeSH Terms
Amino Acid Sequence Animals Binding Sites Chromosomal Proteins, Non-Histone/chemistry,genetics,physiology Chromosomes, Fungal Evolution, Molecular Female Fungal Proteins/chemistry,genetics,physiology Heterochromatin/physiology Humans Molecular Sequence Data Mutagenesis, Site-Directed Nuclear Localization Signals Protein Structure, Quaternary Rats Rats, Inbred F344 Saccharomyces cerevisiae Proteins Schizosaccharomyces/genetics,physiology Transcription Factors/chemistry,genetics,physiology
Chemicals
Cbx1 protein, mouse Chromosomal Proteins, Non-Histone Fungal Proteins Heterochromatin Nuclear Localization Signals SWI6 protein, S cerevisiae Saccharomyces cerevisiae Proteins Transcription Factors
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Wang G
Chromatin Function Laboratory, The Babraham Institute, Babraham, Cambridge, United Kingdom.
Ma A
Chow C M
Horsley D
Brown N R
Cowell I G
Singh P B
References (67)
67 references, click to expand
  1. A knowledge base for predicting protein localization sites in eukaryotic cells.
    Genomics. 1992 Dec;14(4):897-911 PMID: 1478671
  2. Overlapping domains of the heterochromatin-associated protein HP1 mediate nuclear localization and heterochromatin binding.
    J Cell Biol. 1993 Jan;120(2):291-9 PMID: 8421049
  3. Thiamine-repressible expression vectors pREP and pRIP for fission yeast.
    Gene. 1993 Jan 15;123(1):127-30 PMID: 8422996
  4. Regulating genes by packaging domains: bits of heterochromatin in euchromatin?
    Trends Genet. 1993 Feb;9(2):35-7 PMID: 8456498
  5. A mammalian homologue of Drosophila heterochromatin protein 1 (HP1) is a component of constitutive heterochromatin.
    Cytogenet Cell Genet. 1994;66(2):99-103 PMID: 8287692
  6. Switching gene swi6, involved in repression of silent mating-type loci in fission yeast, encodes a homologue of chromatin-associated proteins from Drosophila and mammals.
    Gene. 1994 May 27;143(1):139-43 PMID: 8200530
  7. Telomere-associated chromosome breakage in fission yeast results in variegated expression of adjacent genes.
    EMBO J. 1994 Aug 15;13(16):3801-11 PMID: 8070408
  8. Three additional linkage groups that repress transcription and meiotic recombination in the mating-type region of Schizosaccharomyces pombe.
    Genetics. 1994 Sep;138(1):29-38 PMID: 8001791
  9. Mutations derepressing silent centromeric domains in fission yeast disrupt chromosome segregation.
    Genes Dev. 1995 Jan 15;9(2):218-33 PMID: 7851795
  10. Fission yeast minichromosome loss mutants mis cause lethal aneuploidy and replication abnormality.
    Mol Biol Cell. 1994 Oct;5(10):1145-58 PMID: 7865880
  11. Position effect variegation and chromatin proteins.
    Bioessays. 1992 Sep;14(9):605-12 PMID: 1365916
  12. Heterochromatin protein 1 is required for correct chromosome segregation in Drosophila embryos.
    J Cell Sci. 1995 Apr;108 ( Pt 4):1419-31 PMID: 7615663
  13. The chromodomain protein Swi6: a key component at fission yeast centromeres.
    Science. 1995 Sep 8;269(5229):1429-31 PMID: 7660126
  14. Functional analysis of the chromo domain of HP1.
    EMBO J. 1995 Aug 15;14(16):3977-86 PMID: 7664737
  15. The chromo shadow domain, a second chromo domain in heterochromatin-binding protein 1, HP1.
    Nucleic Acids Res. 1995 Aug 25;23(16):3168-73 PMID: 7667093
  16. Mapping functional domains of the polycomb protein of Drosophila melanogaster.
    Chromosome Res. 1995 Sep;3(6):351-60 PMID: 7551550
  17. Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1.
    J Biol Chem. 1996 Jun 21;271(25):14653-6 PMID: 8663349
  18. KAP-1 corepressor protein interacts and colocalizes with heterochromatic and euchromatic HP1 proteins: a potential role for Krüppel-associated box-zinc finger proteins in heterochromatin-mediated gene silencing.
    Mol Cell Biol. 1999 Jun;19(6):4366-78 PMID: 10330177
  19. Protein modelling for all.
    Trends Biochem Sci. 1999 Sep;24(9):364-7 PMID: 10470037
  20. M31, a murine homolog of Drosophila HP1, is concentrated in the XY body during spermatogenesis.
    Cytogenet Cell Genet. 1999;86(1):83-8 PMID: 10516442
  21. Construction of a Schizosaccharomyces pombe gene bank in a yeast bacterial shuttle vector and its use to isolate genes by complementation.
    Mol Gen Genet. 1982;187(2):326-9 PMID: 6294466
  22. Four mating-type genes control sexual differentiation in the fission yeast.
    EMBO J. 1988 May;7(5):1537-47 PMID: 2900761
  23. Towards an understanding of position effect variegation.
    Dev Genet. 1989;10(3):162-76 PMID: 2500281
  24. Site-directed mutagenesis by overlap extension using the polymerase chain reaction.
    Gene. 1989 Apr 15;77(1):51-9 PMID: 2744487
  25. Characterization of Schizosaccharomyces pombe minichromosome deletion derivatives and a functional allocation of their centromere.
    EMBO J. 1989 Oct;8(10):3045-52 PMID: 2583093
  26. nmt1 of fission yeast. A highly transcribed gene completely repressed by thiamine.
    J Biol Chem. 1990 Jul 5;265(19):10857-64 PMID: 2358444
  27. Mutation in a heterochromatin-specific chromosomal protein is associated with suppression of position-effect variegation in Drosophila melanogaster.
    Proc Natl Acad Sci U S A. 1990 Dec;87(24):9923-7 PMID: 2124708
  28. Two interdependent basic domains in nucleoplasmin nuclear targeting sequence: identification of a class of bipartite nuclear targeting sequence.
    Cell. 1991 Feb 8;64(3):615-23 PMID: 1991323
  29. Interaction with members of the heterochromatin protein 1 (HP1) family and histone deacetylation are differentially involved in transcriptional silencing by members of the TIF1 family.
    EMBO J. 1999 Nov 15;18(22):6385-95 PMID: 10562550
  30. Heterochromatin protein 1 modifies mammalian PEV in a dose- and chromosomal-context-dependent manner.
    Nat Genet. 1999 Dec;23(4):457-61 PMID: 10581035
  31. Mammalian chromodomain proteins: their role in genome organisation and expression.
    Bioessays. 2000 Feb;22(2):124-37 PMID: 10655032
  32. The HP1 chromo shadow domain binds a consensus peptide pentamer.
    Curr Biol. 2000 Jan 13;10(1):27-30 PMID: 10660299
  33. Genes involved in meiosis and sporulation of a yeast.
    Mol Gen Genet. 1968;102(4):301-6 PMID: 5743433
  34. Rat x rat hybrid myelomas and a monoclonal anti-Fd portion of mouse IgG.
    Nature. 1979 Jan 11;277(5692):131-3 PMID: 310519
  35. Spectrin tetramer-dimer equilibrium and the stability of erythrocyte membrane skeletons.
    Nature. 1980 Jun 19;285(5766):586-8 PMID: 6893219
  36. Self-assembly of spectrin oligomers in vitro: a basis for a dynamic cytoskeleton.
    J Cell Biol. 1981 Feb;88(2):463-8 PMID: 7204503
  37. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe.
    Methods Enzymol. 1991;194:795-823 PMID: 2005825
  38. A sequence motif found in a Drosophila heterochromatin protein is conserved in animals and plants.
    Nucleic Acids Res. 1991 Feb 25;19(4):789-94 PMID: 1708124
  39. Mechanisms for the construction and developmental control of heterochromatin formation and imprinted chromosome domains.
    Dev Suppl. 1990;:35-45 PMID: 2090429
  40. Position-effect variegation--an assay for nonhistone chromosomal proteins and chromatin assembly and modifying factors.
    Methods Cell Biol. 1991;35:587-627 PMID: 1685760
  41. Nuclear targeting sequences--a consensus?
    Trends Biochem Sci. 1991 Dec;16(12):478-81 PMID: 1664152
  42. Boundary functions in the control of gene expression.
    Trends Genet. 1991 Oct;7(10):335-40 PMID: 1781031
  43. swi6, a gene required for mating-type switching, prohibits meiotic recombination in the mat2-mat3 "cold spot" of fission yeast.
    Genetics. 1991 Dec;129(4):1033-42 PMID: 1783290
  44. Analysis of the functional role of the Polycomb chromo domain in Drosophila melanogaster.
    Genes Dev. 1992 Jul;6(7):1241-54 PMID: 1628830
  45. Cloning and expression of Drosophila HP1 homologs from a mealybug, Planococcus citri.
    J Cell Sci. 1992 Feb;101 ( Pt 2):463-74 PMID: 1629256
  46. The clr1 locus regulates the expression of the cryptic mating-type loci of fission yeast.
    Genetics. 1992 Jun;131(2):287-96 PMID: 1644273
  47. Heterochromatin protein 1, a known suppressor of position-effect variegation, is highly conserved in Drosophila.
    Nucleic Acids Res. 1992 Nov 25;20(22):6067-74 PMID: 1461737
  48. A probabilistic classification system for predicting the cellular localization sites of proteins.
    Proc Int Conf Intell Syst Mol Biol. 1996;4:109-15 PMID: 8877510
  49. Mutations in the fission yeast silencing factors clr4+ and rik1+ disrupt the localisation of the chromo domain protein Swi6p and impair centromere function.
    J Cell Sci. 1996 Nov;109 ( Pt 11):2637-48 PMID: 8937982
  50. A possible involvement of TIF1 alpha and TIF1 beta in the epigenetic control of transcription by nuclear receptors.
    EMBO J. 1996 Dec 2;15(23):6701-15 PMID: 8978696
  51. Domain-specific interactions of human HP1-type chromodomain proteins and inner nuclear membrane protein LBR.
    J Biol Chem. 1997 Jun 6;272(23):14983-9 PMID: 9169472
  52. Structure of the chromatin binding (chromo) domain from mouse modifier protein 1.
    EMBO J. 1997 May 1;16(9):2473-81 PMID: 9171360
  53. Histone acetylation in chromatin structure and transcription.
    Nature. 1997 Sep 25;389(6649):349-52 PMID: 9311776
  54. The M31 gene has a complex developmentally regulated expression profile and may encode alternative protein products that possess diverse subcellular localisation patterns.
    J Exp Zool. 1998 Mar 1;280(4):288-303 PMID: 9493348
  55. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling.
    Electrophoresis. 1997 Dec;18(15):2714-23 PMID: 9504803
  56. Multiple epigenetic events regulate mating-type switching of fission yeast.
    Novartis Found Symp. 1998;214:87-99; discussion 99-103 PMID: 9601013
  57. The chromo and SET domains of the Clr4 protein are essential for silencing in fission yeast.
    Nat Genet. 1998 Jun;19(2):192-5 PMID: 9620780
  58. Red-shifted excitation mutants of the green fluorescent protein.
    Biotechnology (N Y). 1995 Feb;13(2):151-4 PMID: 9634755
  59. Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment.
    Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7316-21 PMID: 9636146
  60. Chromatin components as part of a putative transcriptional repressing complex.
    Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7322-6 PMID: 9636147
  61. Conspiracy of silence among repeated transgenes.
    Bioessays. 1998 Jul;20(7):532-5 PMID: 9723001
  62. The fission yeast chromo domain encoding gene chp1(+) is required for chromosome segregation and shows a genetic interaction with alpha-tubulin.
    Nucleic Acids Res. 1998 Sep 15;26(18):4222-9 PMID: 9722643
  63. Histone deacetylase homologs regulate epigenetic inheritance of transcriptional silencing and chromosome segregation in fission yeast.
    Genetics. 1998 Oct;150(2):563-76 PMID: 9755190
  64. C-Terminal binding protein is a transcriptional repressor that interacts with a specific class of vertebrate Polycomb proteins.
    Mol Cell Biol. 1999 Jan;19(1):777-87 PMID: 9858600
  65. Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division.
    Mol Cell. 1999 Feb;3(2):207-17 PMID: 10078203
  66. Functional domain structure of human heterochromatin protein HP1(Hsalpha): involvement of internal DNA-binding and C-terminal self-association domains in the formation of discrete dots in interphase nuclei.
    J Biochem. 1999 Apr;125(4):832-7 PMID: 10101299
  67. Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31.
    EMBO J. 1999 Apr 1;18(7):1923-38 PMID: 10202156
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.18.6970-6983.2000
Published
2000-09-00
Pages
6970-83
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC88772
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.20.18.6970-6983.2000 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