Home LiteratureArticle Details
PMID: 16418531 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Coregulated human globin genes are frequently in spatial proximity when active.

The Journal of cell biology ·Vol. 172 ·No. 2 ·2006-01-16 ·Pages 177-87

Brown JM, Leach J, Reittie JE, Atzberger A, Lee-Prudhoe J, Wood WG, Higgs DR, Iborra FJ, Buckle VJ

Abstract

The organization of genes within the nucleus may influence transcription. We have analyzed the nuclear positioning of the coordinately regulated alpha- and beta-globin genes and show that the gene-dense chromatin surrounding the human alpha-globin genes is frequently decondensed, independent of transcription. Against this background, we show the frequent juxtaposition of active alpha- and beta-globin genes and of homologous alpha-globin loci that occurs at nuclear speckles and correlates with transcription. However, we did not see increased colocalization of signals, which would be expected with direct physical interaction. The same degree of proximity does not occur between human beta-globin genes or between murine globin genes, which are more constrained to their chromosome territories. Our findings suggest that the distribution of globin genes within erythroblast nuclei is the result of a self-organizing process, involving transcriptional status, diffusional ability of chromatin, and physical interactions with nuclear proteins, rather than a directed form of higher-order control.

MeSH Terms
Animals Cell Nucleus/metabolism Cell Separation Cells, Cultured Chromosomes Erythroblasts/cytology,physiology Gene Expression Regulation Globins/genetics,metabolism Humans In Situ Hybridization, Fluorescence Mice Transcription, Genetic
Chemicals
Globins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Brown Jill M
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, England, UK.
Leach Joanne
Reittie Joyce E
Atzberger Ann
Lee-Prudhoe Jane
Wood William G
Higgs Douglas R
Iborra Francisco J
Buckle Veronica J
References (56)
56 references, click to expand
  1. Transgenic analysis of a 100-kb human beta-globin cluster-containing DNA fragment propagated as a bacterial artificial chromosome.
    Blood. 1999 Nov 1;94(9):3178-84 PMID: 10556205
  2. Large-scale chromatin organization of the major histocompatibility complex and other regions of human chromosome 6 and its response to interferon in interphase nuclei.
    J Cell Sci. 2000 May;113 ( Pt 9):1565-76 PMID: 10751148
  3. Genomics, gene expression and DNA arrays.
    Nature. 2000 Jun 15;405(6788):827-36 PMID: 10866209
  4. 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
  5. Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16.
    Hum Mol Genet. 2001 Feb 15;10(4):339-52 PMID: 11157797
  6. Comparative genome analysis delimits a chromosomal domain and identifies key regulatory elements in the alpha globin cluster.
    Hum Mol Genet. 2001 Feb 15;10(4):371-82 PMID: 11157800
  7. Protein dynamics: implications for nuclear architecture and gene expression.
    Science. 2001 Feb 2;291(5505):843-7 PMID: 11225636
  8. Subtelomeric chromosome rearrangements are detected using an innovative 12-color FISH assay (M-TEL).
    Nat Med. 2001 Apr;7(4):497-501 PMID: 11283680
  9. Expression of alpha- and beta-globin genes occurs within different nuclear domains in haemopoietic cells.
    Nat Cell Biol. 2001 Jun;3(6):602-6 PMID: 11389446
  10. Nuclear relocation of a transactivator subunit precedes target gene activation.
    Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12120-5 PMID: 11593025
  11. Ineffective erythropoiesis in Stat5a(-/-)5b(-/-) mice due to decreased survival of early erythroblasts.
    Blood. 2001 Dec 1;98(12):3261-73 PMID: 11719363
  12. Subchromosomal positioning of the epidermal differentiation complex (EDC) in keratinocyte and lymphoblast interphase nuclei.
    Exp Cell Res. 2002 Jan 15;272(2):163-75 PMID: 11777341
  13. Disassembly of interchromatin granule clusters alters the coordination of transcription and pre-mRNA splicing.
    J Cell Biol. 2002 Feb 4;156(3):425-36 PMID: 11827980
  14. Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development.
    Science. 2002 Apr 5;296(5565):158-62 PMID: 11935030
  15. The path that RNA takes from the nucleus to the cytoplasm: a trip with some surprises.
    Histochem Cell Biol. 2002 Aug;118(2):95-103 PMID: 12189513
  16. Chromosome positioning in the interphase nucleus.
    Trends Cell Biol. 2002 Sep;12(9):425-32 PMID: 12220863
  17. Nuclear organization in differentiating oligodendrocytes.
    J Cell Sci. 2002 Nov 1;115(Pt 21):4071-9 PMID: 12356912
  18. Gene density and transcription influence the localization of chromatin outside of chromosome territories detectable by FISH.
    J Cell Biol. 2002 Dec 9;159(5):753-63 PMID: 12473685
  19. Sequential entry of components of the gene expression machinery into daughter nuclei.
    Mol Biol Cell. 2003 Mar;14(3):1043-57 PMID: 12631722
  20. Nuclear speckles: a model for nuclear organelles.
    Nat Rev Mol Cell Biol. 2003 Aug;4(8):605-12 PMID: 12923522
  21. A genetic analysis of chromosome territory looping: diverse roles for distal regulatory elements.
    Chromosome Res. 2003;11(5):513-25 PMID: 12971726
  22. Understanding alpha globin gene expression: a step towards effective gene therapy.
    Semin Hematol. 1998 Apr;35(2):93-104 PMID: 9565152
  23. The locus control region is necessary for gene expression in the human beta-globin locus but not the maintenance of an open chromatin structure in erythroid cells.
    Mol Cell Biol. 1998 Oct;18(10):5992-6000 PMID: 9742116
  24. Chromatin interaction mechanism of transcriptional control in vivo.
    EMBO J. 1998 Oct 15;17(20):6020-7 PMID: 9774345
  25. Embryonic stem cell lines derived from human blastocysts.
    Science. 1998 Nov 6;282(5391):1145-7 PMID: 9804556
  26. Intron-independent association of splicing factors with active genes.
    J Cell Biol. 1999 Jun 14;145(6):1133-43 PMID: 10366587
  27. The pattern of replication at a human telomeric region (16p13.3): its relationship to chromosome structure and gene expression.
    Hum Mol Genet. 1999 Aug;8(8):1373-86 PMID: 10400984
  28. Internal organisation of the nucleus: assembly of compartments by macromolecular crowding and the nuclear matrix model.
    Biol Cell. 2004 Oct;96(8):595-601 PMID: 15519694
  29. Topology of genes and nontranscribed sequences in human interphase nuclei.
    Exp Cell Res. 2004 Dec 10;301(2):266-79 PMID: 15530862
  30. Visualization of trans-homolog enhancer-promoter interactions at the Abd-B Hox locus in the Drosophila embryo.
    Dev Cell. 2004 Dec;7(6):925-32 PMID: 15572134
  31. Condensed mitotic chromatin is accessible to transcription factors and chromatin structural proteins.
    J Cell Biol. 2005 Jan 3;168(1):41-54 PMID: 15623580
  32. Interchromosomal associations between alternatively expressed loci.
    Nature. 2005 Jun 2;435(7042):637-45 PMID: 15880101
  33. Clustering of multiple specific genes and gene-rich R-bands around SC-35 domains: evidence for local euchromatic neighborhoods.
    J Cell Biol. 2003 Sep 15;162(6):981-90 PMID: 12975345
  34. Condensed chromatin domains in the mammalian nucleus are accessible to large macromolecules.
    EMBO Rep. 2003 Sep;4(9):861-6 PMID: 12947417
  35. Inheritance of Polycomb-dependent chromosomal interactions in Drosophila.
    Genes Dev. 2003 Oct 1;17(19):2406-20 PMID: 14522946
  36. Nucleolar clustering of dispersed tRNA genes.
    Science. 2003 Nov 21;302(5649):1399-401 PMID: 14631041
  37. Repositioning of muscle-specific genes relative to the periphery of SC-35 domains during skeletal myogenesis.
    Mol Biol Cell. 2004 Jan;15(1):197-206 PMID: 14617810
  38. Promyelocytic leukemia nuclear bodies associate with transcriptionally active genomic regions.
    J Cell Biol. 2004 Feb 16;164(4):515-26 PMID: 14970191
  39. X-chromosome inactivation in mouse embryonic stem cells: analysis of histone modifications and transcriptional activity using immunofluorescence and FISH.
    Methods Enzymol. 2004;376:405-19 PMID: 14975321
  40. The evolutionary dynamics of eukaryotic gene order.
    Nat Rev Genet. 2004 Apr;5(4):299-310 PMID: 15131653
  41. Does looping and clustering in the nucleus regulate gene expression?
    Curr Opin Cell Biol. 2004 Jun;16(3):256-62 PMID: 15145349
  42. Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription.
    Genes Dev. 2004 May 15;18(10):1119-30 PMID: 15155579
  43. Form follows function: The genomic organization of cellular differentiation.
    Genes Dev. 2004 Jun 15;18(12):1371-84 PMID: 15198979
  44. Nascent RNA synthesis in the context of chromatin architecture.
    Chromosome Res. 2004;12(5):439-51 PMID: 15252240
  45. Globin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GATA-2.
    EMBO J. 2004 Jul 21;23(14):2841-52 PMID: 15215894
  46. 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
  47. Transcription-dependent spatial arrangements of CFTR and adjacent genes in human cell nuclei.
    J Cell Biol. 2004 Sep 13;166(6):815-25 PMID: 15364959
  48. Active genes dynamically colocalize to shared sites of ongoing transcription.
    Nat Genet. 2004 Oct;36(10):1065-71 PMID: 15361872
  49. Spatial positioning; a new dimension in genome function.
    Cell. 2004 Oct 15;119(2):153-6 PMID: 15479633
  50. Effect of phenylhydrazine-induced hemolytic anemia on nuclear RNA polymerase activity of the mouse spleen.
    Blood. 1973 Aug;42(2):257-66 PMID: 4793114
  51. Asynchronous DNA replication within the human beta-globin gene locus.
    Proc Natl Acad Sci U S A. 1988 Nov;85(21):8081-5 PMID: 3186709
  52. Proliferation and maturation of human erythroid progenitors in liquid culture.
    Blood. 1989 Jan;73(1):100-3 PMID: 2910352
  53. Cis-acting sequences regulating expression of the human alpha-globin cluster lie within constitutively open chromatin.
    Cell. 1992 May 29;69(5):781-93 PMID: 1591777
  54. Nuclear organization of pre-mRNA processing.
    Curr Opin Cell Biol. 1993 Jun;5(3):442-7 PMID: 8352961
  55. The application of fluorescent in situ hybridization to detect Mbcr/abl fusion in variant Ph chromosomes in CML and ALL.
    Cancer Genet Cytogenet. 1993 Nov;71(1):7-14 PMID: 8275455
  56. Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin.
    Cell. 1997 Dec 12;91(6):845-54 PMID: 9413993
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200507073
Published
2006-01-16
Pages
177-87
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2063548
Subset
IM
Grants
Medical Research Council · MC_U137961143 · United Kingdom
Medical Research Council · MC_U137961144 · United Kingdom
Medical Research Council · MC_U137961145 · United Kingdom
Medical Research Council · MC_U137973816 · United Kingdom
External Links
PubMed source DOI: 10.1083/jcb.200507073 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: [email protected]

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