cis-acting DNA sequence controls glucagon gene expression in pancreatic islet cells.
Our studies show that cis-acting DNA sequences present in the 5'-flanking region are important for the promotion of glucagon gene transcription in islet cell lines. Deletion of all but 292 bp of 5'-flanking sequences results in no major change in the relative magnitude of transcriptional activity in glucagon-producing RIN1056A cells. Moreover, transcriptional activity of the GLUCAT fusion genes is consistently greater in glucagon-producing than in insulin-producing islet cell lines. The cellular specificity of glucagon gene transcription is further emphasized by the lack of transcriptional activity following transfection of non-islet cell lines (BHK, HeLa, and JEG cells) with five different GLUCAT plasmids. These observations suggest that trans-acting factors present in islet cell lines interact with DNA sequences in the 5'-flanking region of the rat glucagon gene to mediate islet cell-specific gene transcription. These studies should provide a useful model for the isolation and characterization of the trans-acting factors important for glucagon gene transcription.
Drucker
D J
DJ
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston.
Philippe
J
J
Jepeal
L
L
Habener
J F
JF
D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D005796:Genes; D005934:Glucagon / Q000235:genetics*; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D010957:Plasmids; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014162:Transfection
D005934:Glucagon