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PMID: 7962047 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Human CENP-A contains a histone H3 related histone fold domain that is required for targeting to the centromere.

The Journal of cell biology ·Vol. 127 ·No. 3 ·1994-11-00 ·Pages 581-92

Sullivan KF, Hechenberger M, Masri K

Abstract

Centromeres are the differentiated chromosomal domains that specify the mitotic behavior of chromosomes. To examine the molecular basis for the specification of centromeric chromatin, we have cloned a human cDNA that encodes the 17-kD histone-like centromere antigen, CENP-A. Two domains are evident in the 140 aa CENP-A polypeptide: a unique NH2-terminal domain and a 93-amino acid COOH-terminal domain that shares 62% identity with nucleosomal core protein, histone H3. An epitope tagged derivative of CENP-A was faithfully targeted to centromeres when expressed in a variety of animal cells and this targeting activity was shown to reside in the histone-like COOH-terminal domain of CENP-A. These data clearly indicate that the assembly of centromeres is driven, at least in part, by the incorporation of a novel core histone into centromeric chromatin.

MeSH Terms
Amino Acid Sequence Animals Autoantigens/chemistry Base Sequence Cattle Centromere/metabolism Centromere Protein A Chromosomal Proteins, Non-Histone/biosynthesis,chemistry,metabolism Cloning, Molecular Fluorescent Antibody Technique HeLa Cells Histones/chemistry,metabolism Humans Immunoblotting Molecular Sequence Data Muntjacs Oligodeoxyribonucleotides Protein Folding Recombinant Fusion Proteins/chemistry Sequence Homology, Amino Acid
Chemicals
Autoantigens CENPA protein, human Centromere Protein A Chromosomal Proteins, Non-Histone Histones Oligodeoxyribonucleotides Recombinant Fusion Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sullivan K F
Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037.
Hechenberger M
Masri K
References (52)
52 references, click to expand
  1. Histone H3 N-terminal mutations allow hyperactivation of the yeast GAL1 gene in vivo.
    EMBO J. 1992 Sep;11(9):3297-306 PMID: 1505519
  2. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  3. Isolation of a yeast centromere and construction of functional small circular chromosomes.
    Nature. 1980 Oct 9;287(5782):504-9 PMID: 6999364
  4. CENP-C, an autoantigen in scleroderma, is a component of the human inner kinetochore plate.
    Cell. 1992 Jul 10;70(1):115-25 PMID: 1339310
  5. A comprehensive compilation and alignment of histones and histone genes.
    Nucleic Acids Res. 1989;17 Suppl:r311-46 PMID: 2654891
  6. CENP-C is required for maintaining proper kinetochore size and for a timely transition to anaphase.
    J Cell Biol. 1994 May;125(3):531-45 PMID: 8175879
  7. Microinjected centromere [corrected] kinetochore antibodies interfere with chromosome movement in meiotic and mitotic mouse oocytes.
    J Cell Biol. 1990 Oct;111(4):1491-504 PMID: 2211822
  8. Kinetochore structure, duplication, and distribution in mammalian cells: analysis by human autoantibodies from scleroderma patients.
    J Cell Biol. 1981 Oct;91(1):95-102 PMID: 7298727
  9. Histone H3 disulfide dimers and nucleosome structure.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5519-23 PMID: 271975
  10. MacroH2A, a core histone containing a large nonhistone region.
    Science. 1992 Sep 4;257(5075):1398-400 PMID: 1529340
  11. The nucleosomal core histone octamer at 3.1 A resolution: a tripartite protein assembly and a left-handed superhelix.
    Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10148-52 PMID: 1946434
  12. Identification of a family of human centromere proteins using autoimmune sera from patients with scleroderma.
    Chromosoma. 1985;91(3-4):313-21 PMID: 2579778
  13. Autoantibody to centromere (kinetochore) in scleroderma sera.
    Proc Natl Acad Sci U S A. 1980 Mar;77(3):1627-31 PMID: 6966403
  14. A 240 kd multisubunit protein complex, CBF3, is a major component of the budding yeast centromere.
    Cell. 1991 Feb 22;64(4):717-25 PMID: 1997204
  15. Microtubule-motor activity of a yeast centromere-binding protein complex.
    Nature. 1992 Oct 8;359(6395):533-6 PMID: 1406970
  16. The fine structure of the kinetochore of a mammalian cell in vitro.
    Chromosoma. 1966;19(1):28-43 PMID: 5912064
  17. Participation of core histone "tails" in the stabilization of the chromatin solenoid.
    J Cell Biol. 1982 May;93(2):285-97 PMID: 7096439
  18. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
    Anal Biochem. 1983 Jul 1;132(1):6-13 PMID: 6312838
  19. Identification of a subdomain of CENP-B that is necessary and sufficient for localization to the human centromere.
    J Cell Biol. 1992 Mar;116(5):1081-93 PMID: 1740467
  20. Histone localization in polytene chromosomes by immunofluorescence.
    J Cell Biol. 1978 Sep;78(3):910-8 PMID: 359571
  21. The highly conserved N-terminal domains of histones H3 and H4 are required for normal cell cycle progression.
    Mol Cell Biol. 1991 Aug;11(8):4111-20 PMID: 2072911
  22. Yeast centromere DNA is in a unique and highly ordered structure in chromosomes and small circular minichromosomes.
    Cell. 1982 Jun;29(2):305-17 PMID: 6288253
  23. Centromeres: an integrated protein/DNA complex required for chromosome movement.
    Annu Rev Cell Biol. 1991;7:311-36 PMID: 1809349
  24. Chromatin digestion with restriction endonucleases reveals 150-160 bp of protected DNA in the centromere of chromosome XIV in Saccharomyces cerevisiae.
    Mol Gen Genet. 1989 Oct;219(1-2):153-60 PMID: 2693939
  25. CENP-B: a major human centromere protein located beneath the kinetochore.
    J Cell Biol. 1990 May;110(5):1475-88 PMID: 2335558
  26. Structure of the nucleosome core particle at 7 A resolution.
    Nature. 1984 Oct 11-17;311(5986):532-7 PMID: 6482966
  27. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  28. A comprehensive set of sequence analysis programs for the VAX.
    Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 PMID: 6546423
  29. Tension, microtubule rearrangements, and the proper distribution of chromosomes in mitosis.
    Chromosoma. 1989 Jun;98(1):33-9 PMID: 2766878
  30. Injection of anticentromere antibodies in interphase disrupts events required for chromosome movement at mitosis.
    J Cell Biol. 1990 Oct;111(4):1519-33 PMID: 2211824
  31. A human centromere protein, CENP-B, has a DNA binding domain containing four potential alpha helices at the NH2 terminus, which is separable from dimerizing activity.
    J Cell Biol. 1992 Dec;119(6):1413-27 PMID: 1469042
  32. Kinetochore components recognized by human autoantibodies are present on mononucleosomes.
    Mol Cell Biol. 1985 Jan;5(1):173-86 PMID: 2580229
  33. Sequences of four mouse histone H3 genes: implications for evolution of mouse histone genes.
    J Mol Evol. 1986;23(3):242-9 PMID: 3027355
  34. Topography of the histone octamer surface: repeating structural motifs utilized in the docking of nucleosomal DNA.
    Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10489-93 PMID: 8248135
  35. Attraction, phasing and neighbour effects of histone octamers on curved DNA.
    J Mol Biol. 1990 Nov 20;216(2):363-74 PMID: 2174975
  36. A human centromere antigen (CENP-B) interacts with a short specific sequence in alphoid DNA, a human centromeric satellite.
    J Cell Biol. 1989 Nov;109(5):1963-73 PMID: 2808515
  37. Cellular substrates of p34(cdc2) and its companion cyclin-dependent kinases.
    Trends Cell Biol. 1993 Sep;3(9):296-301 PMID: 14731846
  38. Primary organization of nucleosome core particle of chromatin: sequence of histone arrangement along DNA.
    Proc Natl Acad Sci U S A. 1978 Sep;75(9):4184-8 PMID: 279907
  39. CENP-B is a highly conserved mammalian centromere protein with homology to the helix-loop-helix family of proteins.
    Chromosoma. 1991 Jul;100(6):360-70 PMID: 1893793
  40. Purification of the centromere-specific protein CENP-A and demonstration that it is a distinctive histone.
    Proc Natl Acad Sci U S A. 1991 May 1;88(9):3734-8 PMID: 2023923
  41. SR alpha promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat.
    Mol Cell Biol. 1988 Jan;8(1):466-72 PMID: 2827008
  42. Effects of DNA sequence and histone-histone interactions on nucleosome placement.
    J Mol Biol. 1990 Nov 5;216(1):69-84 PMID: 2172553
  43. Molecular cloning of cDNA for CENP-B, the major human centromere autoantigen.
    J Cell Biol. 1987 Apr;104(4):817-29 PMID: 2435739
  44. KAR3-encoded kinesin is a minus-end-directed motor that functions with centromere binding proteins (CBF3) on an in vitro yeast kinetochore.
    Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7212-6 PMID: 8041770
  45. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure.
    Proc Natl Acad Sci U S A. 1987 Nov;84(21):7413-7 PMID: 2823261
  46. Structure of the mammalian kinetochore.
    Chromosoma. 1981;82(2):153-70 PMID: 7227036
  47. Acquisition and processing of a conditional dicentric chromosome in Saccharomyces cerevisiae.
    Mol Cell Biol. 1989 Mar;9(3):1368-70 PMID: 2657392
  48. Generation of protein-reactive antibodies by short peptides is an event of high frequency: implications for the structural basis of immune recognition.
    Proc Natl Acad Sci U S A. 1983 Aug;80(16):4949-53 PMID: 6192445
  49. The chromatin structure of centromeres from fission yeast: differentiation of the central core that correlates with function.
    J Cell Biol. 1991 Jan;112(2):191-201 PMID: 1988457
  50. Directional instability of kinetochore motility during chromosome congression and segregation in mitotic newt lung cells: a push-pull mechanism.
    J Cell Biol. 1993 Aug;122(4):859-75 PMID: 8349735
  51. A 17-kD centromere protein (CENP-A) copurifies with nucleosome core particles and with histones.
    J Cell Biol. 1987 Apr;104(4):805-15 PMID: 3558482
  52. 2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans.
    Nature. 1994 Mar 3;368(6466):32-8 PMID: 7906398
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.127.3.581
Published
1994-11-00
Pages
581-92
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2120219
Subset
IM
Grants
NIGMS NIH HHS · GM39068 · United States
Databases
GENBANK
U14518, U14519
External Links
PubMed source DOI: 10.1083/jcb.127.3.581 PMC Full Text View journal details
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