Home LiteratureArticle Details
PMID: 16215742 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Histone lysine methylation patterns in human cell types are arranged in distinct three-dimensional nuclear zones.

Histochemistry and cell biology ·Vol. 125 ·No. 1-2 ·2006-01-00 ·Pages 3-19

Zinner R, Albiez H, Walter J, Peters AH, Cremer T, Cremer M

Abstract

The impact of histone lysine methylation as an essential epigenetic mechanism for gene regulation has been demonstrated by numerous studies where it was functionally and structurally linked to euchromatin and heterochromatin. Most of these data have been obtained by biochemical and two-dimensional (2D)-microscopic techniques providing little information about the global nuclear arrangement of histone modifications. We investigated the 3D architecture and spatial interrelationships of different histone lysine methylation sites (tri-H3K4, mono-H4K20, mono-H3K9, tri-H3K27, tri-H4K20 and tri-H3K9) in various human cell types. Immunofluorescence and confocal microscopy were used together with a quantitative evaluation of 3D images, to reveal spatial relations of specific methylation sites with either centromeres, nascent RNA or with each other. A close association with centromeres was found only for histone methylation sites previously linked to constitutively repressed chromatin. Differences observed in these sites in relation to the cell cycle emphasize the potential relevance of the dynamic properties of heterochromatin for nuclear functions. Nascent RNA was found associated, though to a different degree, with all histone methylation sites, supporting the increasing evidence that transcription occurs across a wide range of the human genome. Finally we demonstrated by simultaneous visualization of different histone lysine methylation sites that methylation patterns are organized in distinct nuclear zones with little apparent intermingling.

MeSH Terms
Algorithms Cell Cycle/physiology Cell Nucleus/metabolism,ultrastructure Cells, Cultured Centromere/metabolism,ultrastructure DNA/biosynthesis,metabolism Female Fibroblasts/metabolism,ultrastructure Histones/metabolism Humans Image Processing, Computer-Assisted Immunohistochemistry Lysine/metabolism Methylation Microscopy, Confocal RNA/biosynthesis,metabolism
Chemicals
Histones RNA DNA Lysine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Zinner Roman
Anthropology and Human Genetics, Department of Biology II, Ludwig-Maximilians-University, Grosshadernerstrasse 2, D-82152, Martinsried, Germany.
Albiez Heiner
Walter Joachim
Peters Antoine H F M
Cremer Thomas
Cremer Marion
References (53)
53 references, click to expand
  1. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin.
    Mol Cell. 2003 Dec;12(6):1577-89 PMID: 14690609
  2. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin.
    Curr Biol. 2003 Jul 15;13(14):1192-200 PMID: 12867029
  3. Histone H3 lysine 4 methylation patterns in higher eukaryotic genes.
    Nat Cell Biol. 2004 Jan;6(1):73-7 PMID: 14661024
  4. Histone methylation versus histone acetylation: new insights into epigenetic regulation.
    Curr Opin Cell Biol. 2001 Jun;13(3):263-73 PMID: 11343896
  5. The indexing potential of histone lysine methylation.
    Novartis Found Symp. 2004;259:22-37; discussion 37-47, 163-9 PMID: 15171245
  6. Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin.
    Nat Cell Biol. 2005 Apr;7(4):420-8 PMID: 15750587
  7. Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes.
    Dev Cell. 2003 Apr;4(4):481-95 PMID: 12689588
  8. Non-random radial arrangements of interphase chromosome territories: evolutionary considerations and functional implications.
    Mutat Res. 2002 Jul 25;504(1-2):37-45 PMID: 12106644
  9. Three dimensional analysis of histone methylation patterns in normal and tumor cell nuclei.
    Eur J Histochem. 2004;48(1):15-28 PMID: 15145772
  10. Plasticity of histone modifications across the invertebrate to vertebrate transition: histone H3 lysine 4 trimethylation in heterochromatin.
    Chromosome Res. 2005;13(1):57-72 PMID: 15791412
  11. The mammalian centromere: structural domains and the attenuation of chromatin modeling.
    FASEB J. 1999 Dec;13 Suppl 2:S216-20 PMID: 10619130
  12. PR-Set7-dependent methylation of histone H4 Lys 20 functions in repression of gene expression and is essential for mitosis.
    Genes Dev. 2005 Feb 15;19(4):431-5 PMID: 15681608
  13. Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution.
    Science. 2005 May 20;308(5725):1149-54 PMID: 15790807
  14. Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin.
    Nat Struct Mol Biol. 2004 Nov;11(11):1076-83 PMID: 15475964
  15. Identification of a family of human centromere proteins using autoimmune sera from patients with scleroderma.
    Chromosoma. 1985;91(3-4):313-21 PMID: 2579778
  16. Automated high through-put colocalization analysis of multichannel confocal images.
    Comput Methods Programs Biomed. 2004 Apr;74(1):63-7 PMID: 14992827
  17. A switch in mitotic histone H4 lysine 20 methylation status is linked to M phase defects upon loss of HCF-1.
    Mol Cell. 2004 Jun 18;14(6):713-25 PMID: 15200950
  18. Colocalization analysis yields superior results after image restoration.
    Microsc Res Tech. 2004 Jun 1;64(2):103-12 PMID: 15352081
  19. Role of histone H3 lysine 27 methylation in X inactivation.
    Science. 2003 Apr 4;300(5616):131-5 PMID: 12649488
  20. The spatio-temporal organization of DNA replication sites is identical in primary, immortalized and transformed mammalian cells.
    J Cell Sci. 2002 Nov 1;115(Pt 21):4037-51 PMID: 12356909
  21. Genetic instabilities in human cancers.
    Nature. 1998 Dec 17;396(6712):643-9 PMID: 9872311
  22. Replication labeling patterns and chromosome territories typical of mammalian nuclei are conserved in the early metazoan Hydra.
    Chromosoma. 2003 Dec;112(4):190-200 PMID: 14615892
  23. The spatial organization of human chromosomes within the nuclei of normal and emerin-mutant cells.
    Hum Mol Genet. 2001 Feb 1;10(3):211-9 PMID: 11159939
  24. Dynamics of three-dimensional replication patterns during the S-phase, analysed by double labelling of DNA and confocal microscopy.
    J Cell Sci. 1992 Nov;103 ( Pt 3):857-62 PMID: 1478975
  25. The profile of repeat-associated histone lysine methylation states in the mouse epigenome.
    EMBO J. 2005 Feb 23;24(4):800-12 PMID: 15678104
  26. A view of interphase chromosomes.
    Science. 1990 Dec 14;250(4987):1533-40 PMID: 2274784
  27. Exploiting nuclear duality of ciliates to analyse topological requirements for DNA replication and transcription.
    J Cell Sci. 2005 Sep 1;118(Pt 17):3973-83 PMID: 16129882
  28. Chromatin architecture of the human genome: gene-rich domains are enriched in open chromatin fibers.
    Cell. 2004 Sep 3;118(5):555-66 PMID: 15339661
  29. Movement of nuclear poly(A) RNA throughout the interchromatin space in living cells.
    Curr Biol. 1999 Mar 25;9(6):285-91 PMID: 10209094
  30. Multiple spatially distinct types of facultative heterochromatin on the human inactive X chromosome.
    Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17450-5 PMID: 15574503
  31. A chromosomal memory triggered by Xist regulates histone methylation in X inactivation.
    PLoS Biol. 2004 Jul;2(7):E171 PMID: 15252442
  32. Recent advances in X-chromosome inactivation.
    Curr Opin Cell Biol. 2004 Jun;16(3):247-55 PMID: 15145348
  33. Chromosome order in HeLa cells changes during mitosis and early G1, but is stably maintained during subsequent interphase stages.
    J Cell Biol. 2003 Mar 3;160(5):685-97 PMID: 12604593
  34. Evolutionary conservation of chromosome territory arrangements in cell nuclei from higher primates.
    Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4424-9 PMID: 11930003
  35. Initial sequencing and comparative analysis of the mouse genome.
    Nature. 2002 Dec 5;420(6915):520-62 PMID: 12466850
  36. A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin.
    Genes Dev. 2004 Jun 1;18(11):1251-62 PMID: 15145825
  37. Histone methyltransferases direct different degrees of methylation to define distinct chromatin domains.
    Mol Cell. 2003 Dec;12(6):1591-8 PMID: 14690610
  38. BRCA1 supports XIST RNA concentration on the inactive X chromosome.
    Cell. 2002 Nov 1;111(3):393-405 PMID: 12419249
  39. Heterochromatin--many flavours, common themes.
    Bioessays. 2005 Jan;27(1):17-28 PMID: 15612037
  40. Dynamic assembly of silent chromatin during thymocyte maturation.
    Nat Genet. 2004 May;36(5):502-6 PMID: 15098035
  41. Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin.
    Mol Cell. 2004 Oct 8;16(1):93-105 PMID: 15469825
  42. Active genes are tri-methylated at K4 of histone H3.
    Nature. 2002 Sep 26;419(6905):407-11 PMID: 12353038
  43. Generation and characterization of methyl-lysine histone antibodies.
    Methods Enzymol. 2004;376:234-54 PMID: 14975310
  44. An epigenetic road map for histone lysine methylation.
    J Cell Sci. 2003 Jun 1;116(Pt 11):2117-24 PMID: 12730288
  45. Non-random radial higher-order chromatin arrangements in nuclei of diploid human cells.
    Chromosome Res. 2001;9(7):541-67 PMID: 11721953
  46. Histone lysine methylation: a signature for chromatin function.
    Trends Genet. 2003 Nov;19(11):629-39 PMID: 14585615
  47. Heterochromatin and tri-methylated lysine 20 of histone H4 in animals.
    J Cell Sci. 2004 May 15;117(Pt 12):2491-501 PMID: 15128874
  48. Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms.
    Bioessays. 2003 Oct;25(10):930-9 PMID: 14505360
  49. Histone hypomethylation is an indicator of epigenetic plasticity in quiescent lymphocytes.
    EMBO J. 2004 Nov 10;23 (22):4462-72 PMID: 15510223
  50. Two-color fluorescence labeling of early and mid-to-late replicating chromatin in living cells.
    Chromosome Res. 2001;9(1):77-80 PMID: 11272795
  51. Genomic maps and comparative analysis of histone modifications in human and mouse.
    Cell. 2005 Jan 28;120(2):169-81 PMID: 15680324
  52. Quantitative digital analysis of diffuse and concentrated nuclear distributions of nascent transcripts, SC35 and poly(A).
    Exp Cell Res. 1997 Feb 25;231(1):27-37 PMID: 9056409
  53. The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote.
    Genes Dev. 2004 Jun 1;18(11):1263-71 PMID: 15175259
Article Info
Journal
Histochemistry and cell biology
Abbr.
Histochem Cell Biol
ISSN
0948-6143
Published
2006-01-00
Epub
2005-00-08
Pages
3-19
Language
English
Region
Germany
NLM ID
9506663
Subset
IM
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: [email protected]