A stepwise epigenetic process controls immunoglobulin allelic exclusion

Nat Rev Immunol. 2004 Oct;4(10):753-61. doi: 10.1038/nri1458.

Abstract

During the differentiation of T and B cells, immune-receptor loci in the genome must be made sterically accessible so that they can undergo rearrangement. Here, we discuss how this is carried out by the stepwise removal of epigenetic repression mechanisms - such as later-replication timing, heterochromatization, histone hypo-acetylation and DNA methylation - in a manner that initially favours one allele in each cell. We propose that this mechanism of allelic exclusion might also be the basis for the generation of gene diversity in other systems.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alleles
  • Antibody Diversity / genetics
  • Cell Differentiation
  • Epigenesis, Genetic*
  • Gene Rearrangement, B-Lymphocyte / genetics*
  • Gene Rearrangement, T-Lymphocyte / genetics*
  • Immunoglobulins / genetics
  • Lymphocytes / cytology*
  • Models, Immunological*

Substances

  • Immunoglobulins