Immunoglobulin kappa enhancers are differentially regulated at the level of chromatin structure.

Full Abstract

The kappa intronic and the kappa 3' enhancers synergize to regulate recombination and transcription of the Ig kappa locus. Although these enhancers have overlapping functions, the kappa i enhancer appears to predominate during receptor editing, while the kappa 3' enhancer may be more important for initiating Ig kappa germline transcription to target locus recombination and, later in development, somatic hypermutation. Changes in chromatin structure appear to regulate both enhancers, and previous reports suggest that both enhancers are packaged into an accessible chromatin structure only in B lineage cells. Why these enhancers cannot activate the demethylated, accessible, protein-associated Ig kappa allele in pro-B cells is not known. Furthermore, how the enhancers function to reactivate the locus for receptor editing or to quantitatively promote hypermutation in B cells is vague. Quantitative analysis of Ig enhancer chromatin structure in murine pro-, pre-and splenic B cells demonstrated that the kappa i enhancer maintains a highly accessible chromatin structure under a variety of conditions. This stable chromatin structure mirrored the highly accessible structure characterizing the Ig mu intronic enhancer, despite the fact that Ig mu is activated prior to Ig kappa during B cell development. Surprisingly, parallel analysis of the kappa 3' enhancer demonstrated its accessible chromatin structure is markedly unstable, as characterized by sensitivity to changes in environmental conditions. These data unexpectedly suggest that kappa locus regulation is compartmentalized along the gene in B lineage cells. Furthermore, these findings raise the possibility that environmentally dependent regulation of kappa 3' enhancer structure underlies changes in kappa activation during B cell development.

Learn Faster Today Improve your study skills

Author information

Author/s: Nikolajczyk, Barbara S (BS); Sardi, Sylvia H (SH); Tumang, Joseph R (JR); Ganley-Leal, Lisa M (LM);

Affiliation: Departments of Microbiology and Medicine, Boston University School of Medicine, Boston, MA 02118, USA. bnikol(-atsign-)bu.edu

Grants: AI60896 (Agency:NIAID NIH HHS) ; R01 AI054611-03 (Agency:NIAID NIH HHS) ; R01 AI054611-04 (Agency:NIAID NIH HHS) ; R01 AI054611-05 (Agency:NIAID NIH HHS) ; R01 AI54611 (Agency:NIAID NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural

Journal: Molecular immunology (Mol Immunol), published in England. (Language: eng)

Reference: 2007-Jul; vol 44 (issue 13) : pp 3407-15

Dates: Created 2007/05/08; Completed 2007/07/31; Revised 2008/11/21;

PMID: 17382392, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article (including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
B-Lymphocyte Subsets - cytology; immunology; metabolism
Cell Differentiation - genetics
Cells, Cultured
Chromatin - chemistry; genetics
Enhancer Elements, Genetic

Gene Expression Regulation - immunology
Immunoglobulin kappa-Chains - genetics
Immunoglobulin mu-Chains - genetics
Mice
Mice, Inbred BALB C
Spleen - cytology; immunology; metabolism

Associated Chemicals: Chromatin (0) ; Immunoglobulin kappa-Chains (0) ; Immunoglobulin mu-Chains (0)

These are the highest related articles currently in the database:

See 100+ related articles.