Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Localized gene-specific induction of accessibility to V(D)J recombination induced by E2A and early B cell factor in nonlymphoid cells

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Goebel, P.
  • Janney, N.
  • Valenzuela, J. R.
  • Romanow, W. J.
  • Murre, C.
  • Feeney, Ann

publication date

  • September 2001

journal

  • Journal of Experimental Medicine  Journal

abstract

  • Accessibility of immunoglobulin (Ig) gene segments to V(D)J recombination is highly regulated and is normally only achieved in B cell precursors. We previously showed that ectopic expression of E2A or early B cell factor (EBF) with recombination activating gene (RAG) induces rearrangement of IgH and IgL genes in nonlymphoid cells. VkappaI genes throughout the locus were induced to rearrange after transfection with E2A, suggesting that the entire Vkappa locus was accessible. However, here we show that Ig loci are not opened globally but that recombination is localized. Gene families are interspersed in the D(H), Vkappa, and Vlambda loci, and we show that certain families and individual genes undergo high levels of recombination after ectopic expression of E2A or EBF, while other families within the same locus are not induced to rearrange. Furthermore, in some families, induction of germline transcription correlates with the level of induced recombination, while in others there is no correlation, suggesting that recombination is not simply initiated by induction of germline transcription. The induced repertoire seen at 24 hours does not change significantly over time indicating the absence of many secondary rearrangements and also suggesting a direct targeting mechanism. We propose that accessibility occurs in a local manner, and that binding sites for factors facilitating accessibility are therefore likely to be associated with individual gene segments.

subject areas

  • Animals
  • B-Lymphocytes
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Line
  • DNA Nucleotidyltransferases
  • DNA-Binding Proteins
  • Gene Rearrangement
  • Genes, Immunoglobulin
  • Genes, RAG-1
  • Homeodomain Proteins
  • Humans
  • Immunoglobulin Variable Region
  • Immunoglobulin kappa-Chains
  • Multigene Family
  • Polymerase Chain Reaction
  • Recombinant Proteins
  • Recombination, Genetic
  • Trans-Activators
  • Transcription Factors
  • Transcription, Genetic
  • Transfection
  • VDJ Recombinases
scroll to property group menus

Research

keywords

  • Igs
  • antibody diversity
  • antibody formation
  • recombination
  • transcription factor
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.194.5.645

PubMed ID

  • 11535632
scroll to property group menus

Additional Document Info

start page

  • 645

end page

  • 656

volume

  • 194

issue

  • 5

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support