Vκ gene repertoire and locus contraction are specified by critical DNase I hypersensitive sites within the Vκ-Jκ intervening region

Yougui Xiang, Sung Kyun Park, William T. Garrard

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The processes of Ig gene locus contraction and looping during V(D)J-recombination are essential for creating a diverse Ab repertoire. However, no cis-acting sequence that plays a major role in specifying locus contraction has been uncovered within the Igκ gene locus. In this article, we demonstrate that a 650-bp sequence corresponding to DNase I hypersensitive sites HS1-2 within the mouse Igκ gene V-J intervening region binds CCCTC-binding factor and specifies locus contraction and long-range Vk gene usage spanning 3.2 Mb in pre-B cells. We call this novel element Cer (for "contracting element for recombination"). Targeted deletion of Cer caused markedly increased proximal and greatly diminished upstream Vk gene usage, higher allele usage, more splenic Igκ+ B cells, and nonlineage-specific Igκ rearrangement in T cells. Relative to wild-type mice, Cer-deletion mice exhibited similar levels of Vk gene germline transcription and H3K4me3 epigenetic marks but displayed a dramatic decrease in locus contraction in pre-B cells. Thus, our studies demonstrate that DNase I hypersensitive sites HS1-2 within the Vk-Jk intervening region are essential for controlling locus contraction and creating a diverse Ab repertoire.

Original languageEnglish (US)
Pages (from-to)1819-1826
Number of pages8
JournalJournal of Immunology
Volume190
Issue number4
DOIs
Publication statusPublished - Feb 15 2013

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ASJC Scopus subject areas

  • Immunology

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