Regulation of a transfected human class II major histocompatibility complex gene in human fibroblasts.

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Abstract
To investigate the cis-acting DNA elements that are involved in regulation of class II major histocompatibility complex genes, including .gamma.-interferon (.gamma.-IFN) induction, 5'' flanking DNA deletions of a DQ.beta. "minigene" were analyzed in stable transfected cell lines. At least four elements 5'' to the gene were found to be involved in DQ.beta. regulation. Deletion of sequences from -2500 to -159 base pairs (bp) resulted in increased transcription, suggesting that negative regulatory elements resided in the deleted region. These clones were all capable of responding to .gamma.-IFN. Further deletion of sequences from -159 to -128 bp resulted in constitutive high level transcription and the inability of these constructions to respond to .gamma.-IFN. A deletion to -107 bp resulted in a decrease in the basal level of expression that was restored by removal of the 5'' DNA sequence to -82 bp, suggesting the presence of a second negative element. Finally, deletion to -64 bp caused a marked decrease in expression, suggesting the loss of an element necessary for high levels of transcription. The .gamma.-IFN control and the transcription control elements contain the conserved upstream sequences found in all class II genes, suggesting a role for these sequences.