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PMID: 12370427 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The origin of a developmentally regulated Igh replicon is located near the border of regulatory domains for Igh replication and expression.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 21 ·2002-10-15 ·Pages 13693-8

Zhou J, Ashouian N, Delepine M, Matsuda F, Chevillard C, Riblet R, Schildkraut CL, Birshtein BK

Abstract

The 3' Ig heavy chain locus (Igh) regulatory region is the most downstream known element of the murine Igh gene cluster. We report here that the nearest non-Igh genes-Crip, Crp2, and Mta1-are located approximately 70 kb further downstream and are beyond the end of the domain of Igh transcriptional regulation. We have localized an origin of replication in MEL cells to a 3-kb segment located between the 3' Igh regulatory region and Crip. Sequences downstream of this origin are replicated by forks that move in both directions. Sequences upstream of this origin (Igh-C, -D, and -J) are replicated in a single direction through a 500-kb segment in which no active bidirectional origins can be detected. We propose that this origin may lie at or near the end of the Igh regulation domain.

MeSH Terms
Animals CCAAT-Enhancer-Binding Protein-beta/genetics Carrier Proteins/genetics Cell Line Chromosomes, Artificial, Bacterial/genetics DNA Replication/genetics Expressed Sequence Tags Gene Expression Regulation Histone Deacetylases Immunoglobulin A/genetics Immunoglobulin Heavy Chains/genetics LIM Domain Proteins Mice Molecular Sequence Data Multigene Family Proteins/genetics Replication Origin Replicon/genetics Repressor Proteins Trans-Activators
Chemicals
CCAAT-Enhancer-Binding Protein-beta CRIP1 protein, human Carrier Proteins Crip1 protein, mouse Immunoglobulin A Immunoglobulin Heavy Chains LIM Domain Proteins Mta1 protein, human Proteins Repressor Proteins Trans-Activators Histone Deacetylases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Zhou Jie
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Ashouian Nasrin
Delepine Marc
Matsuda Fumihiko
Chevillard Christophe
Riblet Roy
Schildkraut Carl L
Birshtein Barbara K
References (52)
52 references, click to expand
  1. PipMaker--a web server for aligning two genomic DNA sequences.
    Genome Res. 2000 Apr;10(4):577-86 PMID: 10779500
  2. Nonequivalent nuclear location of immunoglobulin alleles in B lymphocytes.
    Nat Immunol. 2001 Sep;2(9):848-54 PMID: 11526401
  3. Regulation of cysteine-rich intestinal protein, a zinc finger protein, by mediators of the immune response.
    J Infect Dis. 2000 Sep;182 Suppl 1:S81-4 PMID: 10944488
  4. Cell-cycle-regulated DNA double-stranded breaks in somatic hypermutation of immunoglobulin genes.
    Nature. 2000 Nov 9;408(6809):216-21 PMID: 11089977
  5. DNA double-strand breaks in immunoglobulin genes undergoing somatic hypermutation.
    Immunity. 2000 Nov;13(5):589-97 PMID: 11114372
  6. Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor.
    Nat Cell Biol. 2001 Jan;3(1):30-7 PMID: 11146623
  7. A pivotal role for DNase I-sensitive regions 3b and/or 4 in the induction of somatic hypermutation of IgH genes.
    J Immunol. 2001 Jul 15;167(2):811-20 PMID: 11441087
  8. Chromatin remodeling at the Ig loci prior to V(D)J recombination.
    J Immunol. 2001 Jul 15;167(2):866-74 PMID: 11441093
  9. Differential expression and subcellular distribution of the mouse metastasis-associated proteins Mta1 and Mta3.
    Gene. 2001 Jul 25;273(1):29-39 PMID: 11483358
  10. Localization of the 3' IgH locus elements that effect long-distance regulation of class switch recombination.
    Immunity. 2001 Aug;15(2):187-99 PMID: 11520455
  11. Ablation of XRCC2/3 transforms immunoglobulin V gene conversion into somatic hypermutation.
    Nature. 2001 Aug 30;412(6850):921-6 PMID: 11528482
  12. Hypermutation: give us a break.
    Nat Immunol. 2001 Oct;2(10):902-3 PMID: 11577343
  13. Making sense of eukaryotic DNA replication origins.
    Science. 2001 Oct 5;294(5540):96-100 PMID: 11588251
  14. Asynchronous replication and allelic exclusion in the immune system.
    Nature. 2001 Nov 8;414(6860):221-5 PMID: 11700561
  15. Stepwise activation of the immunoglobulin mu heavy chain gene locus.
    EMBO J. 2001 Nov 15;20(22):6394-403 PMID: 11707410
  16. Replication initiation patterns in the beta-globin loci of totipotent and differentiated murine cells: evidence for multiple initiation regions.
    Mol Cell Biol. 2002 Jan;22(2):442-52 PMID: 11756541
  17. Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development.
    Science. 2002 Apr 5;296(5565):158-62 PMID: 11935030
  18. Initiation sites are distributed at frequent intervals in the Chinese hamster dihydrofolate reductase origin of replication but are used with very different efficiencies.
    Mol Cell Biol. 2002 May;22(9):3053-65 PMID: 11940663
  19. Replication and subnuclear location dynamics of the immunoglobulin heavy-chain locus in B-lineage cells.
    Mol Cell Biol. 2002 Jul;22(13):4876-89 PMID: 12052893
  20. Replication timing and transcriptional control: beyond cause and effect.
    Curr Opin Cell Biol. 2002 Jun;14(3):377-83 PMID: 12067662
  21. Developmental regulation of a gene that encodes a cysteine-rich intestinal protein and maps near the murine immunoglobulin heavy chain locus.
    Proc Natl Acad Sci U S A. 1986 Apr;83(8):2516-20 PMID: 3085096
  22. Myeloma mutant with a novel 3' flanking region: loss of normal sequence and insertion of repetitive elements leads to decreased transcription but normal processing of the alpha heavy-chain gene products.
    Mol Cell Biol. 1986 Jun;6(6):1903-16 PMID: 3023910
  23. Rate of replication of the murine immunoglobulin heavy-chain locus: evidence that the region is part of a single replicon.
    Mol Cell Biol. 1987 Jan;7(1):450-7 PMID: 3031474
  24. Replication program of active and inactive multigene families in mammalian cells.
    Mol Cell Biol. 1988 May;8(5):2149-58 PMID: 3386634
  25. An initiation zone of chromosomal DNA replication at the chicken lysozyme gene locus.
    J Biol Chem. 1998 Jul 17;273(29):18300-7 PMID: 9660795
  26. NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities.
    Mol Cell. 1998 Dec;2(6):851-61 PMID: 9885572
  27. The fission yeast homologue of Orc4p binds to replication origin DNA via multiple AT-hooks.
    Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2656-61 PMID: 10077566
  28. Evidence that a single replication fork proceeds from early to late replicating domains in the IgH locus in a non-B cell line.
    Mol Cell. 1999 Mar;3(3):321-30 PMID: 10198634
  29. Orientation of DNA replication establishes mating-type switching pattern in S. pombe.
    Nature. 1999 Jul 8;400(6740):181-4 PMID: 10408447
  30. One of the tightly clustered genes of the mouse surfeit locus is a highly expressed member of a multigene family whose other members are predominantly processed pseudogenes.
    Mol Cell Biol. 1988 Sep;8(9):3898-905 PMID: 3221868
  31. Ribosomal protein L7a is encoded by a gene (Surf-3) within the tightly clustered mouse surfeit locus.
    Mol Cell Biol. 1989 Jan;9(1):224-31 PMID: 2648130
  32. Replication forks are associated with the nuclear matrix.
    Nucleic Acids Res. 1990 Apr 25;18(8):1965-9 PMID: 2336385
  33. The HOX-5 and surfeit gene clusters are linked in the proximal portion of mouse chromosome 2.
    Genomics. 1990 Apr;6(4):645-50 PMID: 1971250
  34. The mouse immunoglobulin kappa light-chain genes are located in early- and late-replicating regions of chromosome 6.
    Mol Cell Biol. 1990 Aug;10(8):4314-23 PMID: 2115125
  35. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  36. Mapping of replication initiation sites in mammalian genomes by two-dimensional gel analysis: stabilization and enrichment of replication intermediates by isolation on the nuclear matrix.
    Mol Cell Biol. 1991 Aug;11(8):3850-9 PMID: 2072896
  37. A linkage map of distal mouse chromosome 12.
    Mamm Genome. 1991;1(1):30-6 PMID: 1794043
  38. DNA regions flanking the mouse Ig 3' alpha enhancer are differentially methylated and DNAase I hypersensitive during B cell differentiation.
    J Immunol. 1993 Mar 1;150(5):1772-80 PMID: 8436815
  39. Initiation and termination of DNA replication in human rRNA genes.
    Mol Cell Biol. 1993 Oct;13(10):6600-13 PMID: 8413256
  40. Cloning of CRP2, a novel member of the cysteine-rich protein family with two repeats of an unusual LIM/double zinc-finger motif.
    FEBS Lett. 1993 Oct 25;333(1-2):51-5 PMID: 8224170
  41. A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses.
    J Biol Chem. 1994 Sep 16;269(37):22958-63 PMID: 8083195
  42. Identification of 3' alpha-hs4, a novel Ig heavy chain enhancer element regulated at multiple stages of B cell differentiation.
    Nucleic Acids Res. 1995 Mar 25;23(6):975-81 PMID: 7731812
  43. Immunoglobulin gene transcription ceases upon deletion of a distant enhancer.
    EMBO J. 1995 Dec 15;14(24):6229-38 PMID: 8557042
  44. Palindromic structure of the IgH 3'locus control region.
    Nat Genet. 1996 Sep;14(1):15-6 PMID: 8782813
  45. Human ESP1/CRP2, a member of the LIM domain protein family: characterization of the cDNA and assignment of the gene locus to chromosome 14q32.3.
    Genomics. 1996 Jan 15;31(2):167-76 PMID: 8824798
  46. A novel cDNA encoding for a LIM domain protein located at human chromosome 14q32 as a candidate for leukemic translocation.
    Biochem Mol Biol Int. 1996 Jul;39(4):747-54 PMID: 8843343
  47. Structure and expression of two highly related genes encoding SCM-1/human lymphotactin.
    FEBS Lett. 1996 Oct 14;395(1):82-8 PMID: 8849694
  48. Dyad symmetry within the mouse 3' IgH regulatory region includes two virtually identical enhancers (C alpha3'E and hs3).
    J Immunol. 1997 May 15;158(10):4780-7 PMID: 9144492
  49. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
    Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 PMID: 9254694
  50. Regulation of the replication of the murine immunoglobulin heavy chain gene locus: evaluation of the role of the 3' regulatory region.
    Mol Cell Biol. 1997 Oct;17(10):6167-74 PMID: 9315677
  51. Deletional analyses reveal an essential role for the hs3b/hs4 IgH 3' enhancer pair in an Ig-secreting but not an earlier-stage B cell line.
    Int Immunol. 2001 Aug;13(8):1003-12 PMID: 11470770
  52. The 3' IgH regulatory region: a complex structure in a search for a function.
    Adv Immunol. 2000;75:317-45 PMID: 10879288
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.212392399
Published
2002-10-15
Epub
2002-00-07
Pages
13693-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC129745
Subset
IM
Grants
NIAID NIH HHS · R01 AI023548 · United States
NIAID NIH HHS · AI 23548 · United States
NIGMS NIH HHS · GM 45751 · United States
NIAID NIH HHS · AI 13509 · United States
NIAID NIH HHS · R37 AI013509 · United States
NIAID NIH HHS · R01 AI013509 · United States
NIGMS NIH HHS · R01 GM045751 · United States
Databases
GENBANK
AF450245, AF463504
External Links
PubMed source DOI: 10.1073/pnas.212392399 PMC Full Text View journal details
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