| First Author | Xiang Y | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 4 | Pages | 1819-26 |
| PubMed ID | 23296705 | Mgi Jnum | J:193015 |
| Mgi Id | MGI:5467424 | Doi | 10.4049/jimmunol.1203127 |
| Citation | Xiang Y, et al. (2013) Vkappa Gene Repertoire and Locus Contraction Are Specified by Critical DNase I Hypersensitive Sites within the Vkappa-Jkappa Intervening Region. J Immunol 190(4):1819-26 |
| abstractText | 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 Igkappa gene locus. In this article, we demonstrate that a 650-bp sequence corresponding to DNase I hypersensitive sites HS1-2 within the mouse Igkappa gene V-J intervening region binds CCCTC-binding factor and specifies locus contraction and long-range Vkappa 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 Vkappa gene usage, higher allele usage, more splenic Igkappa(+) B cells, and nonlineage-specific Igkappa rearrangement in T cells. Relative to wild-type mice, Cer-deletion mice exhibited similar levels of Vkappa 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 Vkappa-Jkappa intervening region are essential for controlling locus contraction and creating a diverse Ab repertoire. |
