Cis-regulatory elements and epigenetic changes control genomic rearrangements of the IgH locus

Adv Immunol. 2008:99:1-32. doi: 10.1016/S0065-2776(08)00601-9.

Abstract

Immunoglobulin variable region exons are assembled from discontinuous variable (V), diversity (D), and joining (J) segments by the process of V(D)J recombination. V(D)J rearrangements of the immunoglobulin heavy chain (IgH) locus are tightly controlled in a tissue-specific, ordered and allele-specific manner by regulating accessibility of V, D, and J segments to the recombination activating gene proteins which are the specific components of the V(D)J recombinase. In this review we discuss recent advances and established models brought forward to explain the mechanisms underlying accessibility control of V(D)J recombination, including research on germline transcripts, spatial organization, and chromatin modifications of the immunoglobulin heavy chain (IgH) locus. Furthermore, we review the functions of well-described and potential new cis-regulatory elements with regard to processes such as V(D)J recombination, allelic exclusion, and IgH class switch recombination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromatin / genetics
  • Chromatin / immunology
  • Epigenesis, Genetic*
  • Exons / genetics
  • Exons / immunology
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain / genetics*
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain / immunology
  • Genes, Immunoglobulin / genetics
  • Genes, Immunoglobulin / immunology
  • Humans
  • Immunoglobulin Class Switching / genetics*
  • Immunoglobulin Class Switching / immunology
  • Recombination, Genetic / genetics*
  • Recombination, Genetic / immunology
  • Regulatory Sequences, Nucleic Acid / genetics*
  • Regulatory Sequences, Nucleic Acid / immunology
  • Somatic Hypermutation, Immunoglobulin / genetics
  • Somatic Hypermutation, Immunoglobulin / immunology
  • VDJ Recombinases / genetics*
  • VDJ Recombinases / immunology

Substances

  • Chromatin
  • VDJ Recombinases