AML and Ets proteins regulate the l alpha 1 germ-line promoter

The immunoglobulin heavy chain (IgH) class switch recombination of B lympho cytes preferentially targets unrearranged IgH genes that have already been rendered transcriptionally active. Transcription of the germ-line IgH genes is controlled by intervening (I) regions upstream of their switch regions. The I alpha 1 promoter activates transcription of the human germ-line C al pha 1 gene for IgA1 and mediates the transforming growth factor (TGF)-beta 1 responsiveness of this locus. Here we show that the I alpha 1 promoter co ntains several binding sites for the AML/PEBP2/CBF family of transcription factors and that AML and Ets proteins are major regulators of the basal and TGF-beta-inducible promoter activity. Our data constitute a starting point for studies to elucidate the molecular mechanism by which TGF-beta regulat es IgA production.