The 100-base pair ELA1 transcriptional enhancer drives high level transcrip
tion to pancreatic acinar cells of transgenic mice and in transfected pancr
eatic acinar cells in culture. The A element within the enhancer is the sol
e positively acting element for acinar specificity. We show that the acinar
cell-specific bHLH protein PTF1-P48 and the common bHLH cofactor HEB are p
art of the PTF1 complex that binds the A element and mediates its activity.
Acinar-like activity of the enhancer can be reconstituted in HeLa cells by
the introduction of P48, HEB, and the PDX1-containing trimeric homeodomain
complex that binds the second pancreatic element of the enhancer. The 5' r
egion of the mouse Ptf1-p48 gene from -12.5 to +0.2 kilobase pairs contains
the regulatory information to direct expression in transgenic mice to the
pancreas and other organs of the gat that express the endogenous Ptf1-p48 g
ene. The 5'-flanking sequence contains two activating regions, one of which
is specific for acinar cells, and a repressing domain active in non-pancre
atic cells. Comparison of the 5'-gene flanking regions of the mouse, rat, a
nd human genes identified conserved sequence blocks containing binding site
s for known gut transcription factors within the acinar cell-specific contr
ol region.