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Involvement of a second lymphoid-specific enhancer element in the regulation of immunoglobulin heavy-chain gene expression

Journal Article · · Molecular and Cellular Biology; (USA)
;  [1];  [2]
  1. Massachusetts Inst. of Tech., Cambridge, MA (USA). Dept. of Biology
  2. Lab. of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD (US)
To determine whether enhancer elements in addition to the highly conserved octamer (OCTA)-nucleotide motif are important for lymphoid-specific expression of the immunoglobulin heavy-chain (IgH) gene, the authors have investigated the effect of mutating the binding site for a putative additional lymphoid-specific transcription factor, designated NF-{mu}B, in the murine IgH enhancer. They demonstrate that the NF-{mu}B-binding site plays a critical role in the IgH enhancer, because mutation of the {mu}B DNA motif decreased transcriptional activity of the IgH enhancer in cells of the B-cell lineage but not in nonlymphoid cells. This effect was comparable to or even stronger than the effect of a mutation in the OCTA site.Moreover, combined mutation of both {mu}B and OCTA sites further reduced enhancer activity in lymphoid cells. Alteration of either the {mu}B or E3 site in a 70-base pair fragment of the IgH enhancer that lacks the binding site for OCTA abolished enhancer activity in lymphoid cells completely.
OSTI ID:
6511414
Journal Information:
Molecular and Cellular Biology; (USA), Journal Name: Molecular and Cellular Biology; (USA) Vol. 10:6; ISSN 0270-7306; ISSN MCEBD
Country of Publication:
United States
Language:
English