A new hypersensitive site, HS10, and the enhancers, E3′ and ED, differentially regulate IGκ gene expression

Xiaorong Zhou, Yougui Xiang, Xiaoling Ding, William T. Garrard

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The mouse Igκ gene locus has three known transcriptional enhancers: an intronic enhancer (Ei), a 3′ enhancer (E3′), and a further downstream enhancer (Ed). We previously discovered, using the chromosome conformation-capture technique, that Ei and E3′ interact with a novel DNA sequence near the 3′ end of the Igκ locus, specifically in B cells. In the present investigation, we examined the function of this far downstream element. The sequence is evolutionarily conserved and exhibits a plasmacytoma cellspecific DNase I-hypersensitive site in chromatin, henceforth termed HS10 in the locus. HS10 acts as a coactivator of E3′ in transient transfection assays. Although HS10 -/- mice exhibited normal patterns of B cell development, they were tested further along with E3′ -/- and Ed -/- mice for their Igκ expression levels in plasma cells, as well as for both allelic and isotype exclusion in splenic B cells. HS10 -/- and Ed -/-, but not E3′ -/-, mice exhibited 2.5-fold lower levels of Igκ expression in antigenically challenged plasma cells. E3′ -/- mice, but not HS10′ -/- mice, exhibited impaired IgL isotype and allelic exclusion in splenic B cells. We have suggestive results that Ed may also weakly participate in these processes. In addition, HS10′ -/- mice no longer exhibited regional chromosome interactions with E3′, and they exhibited modestly reduced somatic hypermutation in the Jκ-Cκ intronic region in germinal center B cells from Peyer's patches.We conclude that the HS10, E3′, and Ed differentially regulate Igκ gene dynamics.

Original languageEnglish (US)
Pages (from-to)2722-2732
Number of pages11
JournalJournal of Immunology
Volume188
Issue number6
DOIs
StatePublished - Mar 15 2012

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Gene Expression
B-Lymphocytes
Immunoglobulin Genes
Plasma Cells
Chromosomes
Peyer's Patches
Germinal Center
Plasmacytoma
Deoxyribonuclease I
Chromatin
Transfection

ASJC Scopus subject areas

  • Immunology

Cite this

A new hypersensitive site, HS10, and the enhancers, E3′ and ED, differentially regulate IGκ gene expression. / Zhou, Xiaorong; Xiang, Yougui; Ding, Xiaoling; Garrard, William T.

In: Journal of Immunology, Vol. 188, No. 6, 15.03.2012, p. 2722-2732.

Research output: Contribution to journalArticle

Zhou, Xiaorong ; Xiang, Yougui ; Ding, Xiaoling ; Garrard, William T. / A new hypersensitive site, HS10, and the enhancers, E3′ and ED, differentially regulate IGκ gene expression. In: Journal of Immunology. 2012 ; Vol. 188, No. 6. pp. 2722-2732.
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