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Cutting edge: Developmental stage-specific recruitment of cohesin to CTCF sites throughout immunoglobulin loci during B lymphocyte development

Academic Article
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Overview

authors

  • Degner, S. C.
  • Wong, T. P.
  • Jankevicius, G.
  • Feeney, Ann

publication date

  • January 2009

journal

  • Journal of Immunology  Journal

abstract

  • Contraction of the large Igh and Igkappa loci brings all V genes, spanning >2.5 Mb in each locus, in proximity to DJ(H) or J(kappa) genes. CCCTC-binding factor (CTCF) is a transcription factor that regulates gene expression by long-range chromosomal looping. We therefore hypothesized that CTCF may be crucial for the contraction of the Ig loci, but no CTCF sites have been described in any V loci. Using ChIP-chip, we demonstrated many CTCF sites in the V(H) and V(kappa) regions. However, CTCF enrichment in the Igh locus, but not the Igkappa locus, was largely unchanged throughout differentiation, suggesting that CTCF binding alone cannot be responsible for stage-specific looping. Because cohesin can colocalize with CTCF, we performed chromatin immunoprecipitation for the cohesin subunit Rad21 and found lineage and stage-specific Rad21 recruitment to CTCF in all Ig loci. The differential binding of cohesin to CTCF sites may promote multiple loop formation and thus effective V(D)J recombination.

subject areas

  • Animals
  • B-Lymphocytes
  • Binding Sites, Antibody
  • Cell Cycle Proteins
  • Cell Differentiation
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Gene Rearrangement, B-Lymphocyte
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Joining Region
  • Immunoglobulin Variable Region
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nuclear Proteins
  • Phosphoproteins
  • Protein Transport
  • Repressor Proteins
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Identity

PubMed Central ID

  • PMC2625297

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 19109133
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Additional Document Info

start page

  • 44

end page

  • 48

volume

  • 182

issue

  • 1

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