Journal
NUCLEIC ACIDS RESEARCH
Volume 41, Issue 14, Pages 6905-6916Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkt491
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Funding
- Dutch Scientific Organization (NWO) [935170621]
- European Research Council [209700, '4C']
- European Research Council (ERC) [209700] Funding Source: European Research Council (ERC)
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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 V-H regions of both IgH alleles position themselves away from active chromatin. This, we speculate, may help to restrict enhancer activity to the productively rearranged V-H promoter element.
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