A developmental-specific factor binds to suppressor sites flanking the immunoglobulin heavy-chain enhancer.
We identified a novel nuclear protein, NF-mu NR, that binds to multiple sites flanking the immunoglobulin heavy-chain enhancer. The expression of NF-mu NR shows a unique developmental pattern; the activity is present in all cells representing early stages of B-cell development, but is absent from more mature cells that express a high level of immunoglobulin heavy chains. NF-mu NR also is present in most cell lines outside of the B-cell lineage (e.g., T cells, macrophages, and fibroblasts). The binding sites for NF-mu NR correlate very well with cis-acting negative regulatory elements of the heavy-chain enhancer defined previously. Indeed, when the segments bound by NF-mu NR are deleted from the enhancer, it is now found to function as a positive transcription element in T cells and macrophages. Taken together, these results suggest that NF-mu NR may function as a negative regulator of enhancer function. The observation that the segments bound by NF-mu NR correspond to the segments bound to the nuclear matrix suggests an intriguing model not only of how enhancers might function but also of how negative regulation might occur.
Scheuermann
R H
RH
Basel Institute for Immunology, Switzerland.
Chen
U
U
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D006128:Growth; D008957:Models, Genetic; D008969:Molecular Sequence Data; D013489:Suppression, Genetic
D004268:DNA-Binding Proteins; D004247:DNA