Details

Autor(en) / Beteiligte

• Schultz, Cynthia L.
• Elenich, Laura A.
• Dunnick, Wesley A.

Titel

Nuclear protein binding to octamer motifs in the immunoglobulin γ1 switch region

Ist Teil von

• International immunology, 1991-02, Vol.3 (2), p.109-116

Ort / Verlag

Oxford University Press

Erscheinungsjahr

1991

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Initiation of the Immunoglobulin heavy chain switch DNA rearrangement event is thought to involve conversion of the target switch region DNA to an accessible state. Accessibility is likely to be mediated by the binding of regulatory proteinsto sequences in or near switch regions. A DNase hypersensitlvity assay was used to recognize possible regions of protein binding in the γ1 switch region of the B cell hybridoma 470.25. A strong DNase hypersensitive site was identified 5'of the tandemly repeated Sγ1 sequences. Data from other laboratories suggest that this hypersensitive siteis associated with switch recombination to γ1 However, the 470.25 cell does not express the γ1 germllne transcript. A second group of DNase hypersensitive sites within the repetitive portion of the γ1 switch region was alsoidentified. A gel retardation assay for protein - DNA interaction revealed a sequence present in several copies in the γ1 switch region that specifically binds nuclear proteins. This binding sequence, SG1BS, contains the octanucleotide sequence ATGCAAAA, a 7/8 match to the transcrlptlonal enhancer octamer motif found in immunoglobulin promoters and the heavy chain enhancer. Binding competition studies of SG1BS demonstrate that both the octamer and flanking sequences are critical for binding. By size- and tissue-distribution, the factors that bind SG1BS are not distinguishable from the previously identified octamer-binding factors OTF-1 and OTF-2. The ability of proteins to bind the Sγ1 octamer motifis increased 2.3-fold upon IL-4 induction of lipopolysaccharide-stlmulated B cells.