Subnuclear Compartmentalization of Immunoglobulin Loci During Lymphocyte Development

Author:

Kosak Steven T.1,Skok Jane A.2,Medina Kay L.1,Riblet Roy3,Le Beau Michelle M.4,Fisher Amanda G.2,Singh Harinder1

Affiliation:

1. Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute,

2. Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, UK.

3. Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA.

4. Department of Medicine, University of Chicago, Chicago, IL 60637, USA.

Abstract

Immunoglobulin (Ig) loci are selectively activated for transcription and rearrangement during B lymphocyte development. Using fluorescence in situ hybridization, we show that Ig heavy (H) and Igκ loci are preferentially positioned at the nuclear periphery in hematopoietic progenitors and pro-T cells but are centrally configured in pro-B nuclei. The inactive loci at the periphery do not associate with centromeric heterochromatin. Upon localization away from the nuclear periphery in pro-B cells, the IgH locus appears to undergo large-scale compaction. We suggest that subnuclear positioning represents a novel means of regulating transcription and recombination of IgH and Igκ loci during lymphocyte development.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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