Allelic Exclusion of the Immunoglobulin Heavy Chain Locus is Independent of Its Nuclear Localization in Mature B Cells

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2013 Jun 11

PMID 23748562

Citations 21

Authors

Sjoerd J B Holwerda

Harmen J G van de Werken

Claudia Ribeiro de Almeida

Ingrid M Bergen

Marjolein J W de Bruijn

Marjon J A M Verstegen

Marieke Simonis

Erik Splinter

Patrick J Wijchers

Rudi W Hendriks

Wouter de Laat

Affiliations

Soon will be listed here.

Abstract

In developing B cells, the immunoglobulin heavy chain (IgH) locus is thought to move from repressive to permissive chromatin compartments to facilitate its scheduled rearrangement. In mature B cells, maintenance of allelic exclusion has been proposed to involve recruitment of the non-productive IgH allele to pericentromeric heterochromatin. Here, we used an allele-specific chromosome conformation capture combined with sequencing (4C-seq) approach to unambigously follow the individual IgH alleles in mature B lymphocytes. Despite their physical and functional difference, productive and non-productive IgH alleles in B cells and unrearranged IgH alleles in T cells share many chromosomal contacts and largely reside in active chromatin. In brain, however, the locus resides in a different repressive environment. We conclude that IgH adopts a lymphoid-specific nuclear location that is, however, unrelated to maintenance of allelic exclusion. We additionally find that in mature B cells-but not in T cells-the distal VH regions of both IgH alleles position themselves away from active chromatin. This, we speculate, may help to restrict enhancer activity to the productively rearranged VH promoter element.

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