CHARACTERIZATION OF THE ENHANCER REGION FOR GERMLINE TRANSCRIPTION OF THE GAMMA-3 CONSTANT REGION GENE OF HUMAN-IMMUNOGLOBULIN

A constant region gene (C) of the immunoglobulin heavy chain can be transcribed as germline transcripts from a promoter located upstream of a switch region. We have studied the structure and function of the human C-gamma-3 promoter region. When the human IgM-producing cell line SSK41 is stimulated with interleukin 4 (IL-4) in the presence of phorbol myristate acetate (PMA) or Staphylococcus aureus Cowan I, expression of germline C-gamma-3 transcripts was specifically augmented within 4 h. Upstream DNA fragments flanking the I-gamma-3 exon were fused with a reporter gene and tested for IL-4-induced promoter/enhancer activity by transfection of SSK41 cells. The DNA fragment between 450 and 250 bp upstream of the transcription initiation site of the C-gamma-3 gene was shown to be required for transcriptional up-regulation by PMA and IL-4. The upstream 514 bp fragment of the I-gamma-3 flanking region was shown to contain an enhancer activity in response to PMA and IL-4.