A promoter element that exerts positive and negative control of the interleukin 2-responsive J-chain gene.
In a primary immune response a signal from interleukin 2 (IL-2) induces B lymphocytes to express the gene for the IgM joining component, the J chain. The signaling mechanism was pursued in this study by examining the J-chain gene 5' flanking region for regulatory sequences and interacting nuclear factors. The analyses identified a major control region located between -75 and -45 that encodes two adjacent elements: a T-rich sequence (JA) containing a single positive regulatory motif and an A+G-rich sequence (JB) containing overlapping positive and negative regulatory motifs. Dissection of the two elements indicated that the bifunctional JB sequence is the likely target of the IL-2 signal. The evidence was based on findings that (i) JB activity correlated with J-chain gene transcription--i.e., JB acts as a repressor in J-chain-silent B cells and as an activator in J-chain-expressing cells, and (ii) JB activator function is mediated by a B-cell-specific nuclear protein, NF-JB, that exhibits an IL-2-responsive binding pattern.
Lansford
R D
RD
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
McFadden
H J
HJ
Siu
S T
ST
Cox
J S
JS
Cann
G M
GM
Koshland
M E
ME
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005803:Genes, Immunoglobulin; D007144:Immunoglobulin J-Chains / Q000235:genetics*; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid
D004268:DNA-Binding Proteins; D007144:Immunoglobulin J-Chains; D007376:Interleukin-2; D009687:Nuclear Proteins