TY - JOUR
T1 - The Role of PTF1-P48 in Pancreatic Acinar Gene Expression
AU - Rose, Scott D.
AU - Swift, Galvin H
AU - Peyton, Michael J.
AU - Hammer, Robert E
AU - MacDonald, Raymond J
PY - 2001/11/23
Y1 - 2001/11/23
N2 - The 100-base pair ELA1 transcriptional enhancer drives high level transcription to pancreatic acinar cells of transgenic mice and in transfected pancreatic acinar cells in culture. The A element within the enhancer is the sole positively acting element for acinar specificity. We show that the acinar cell-specific bHLH protein PTF1-P48 and the common bHLH cofactor HEB are part 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′ region 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 gut that express the endogenous Ptf1-p48 Ptf7-p48 gene. The 5′-flanking sequence contains two activating regions, one of which is specific for acinar cells, and a repressing domain active in non-pancreatic cells. Comparison of the 5′-gene flanking regions of the mouse, rat, and human genes identified conserved sequence blocks containing binding sites for known gut transcription factors within the acinar cell-specific control region.
AB - The 100-base pair ELA1 transcriptional enhancer drives high level transcription to pancreatic acinar cells of transgenic mice and in transfected pancreatic acinar cells in culture. The A element within the enhancer is the sole positively acting element for acinar specificity. We show that the acinar cell-specific bHLH protein PTF1-P48 and the common bHLH cofactor HEB are part 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′ region 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 gut that express the endogenous Ptf1-p48 Ptf7-p48 gene. The 5′-flanking sequence contains two activating regions, one of which is specific for acinar cells, and a repressing domain active in non-pancreatic cells. Comparison of the 5′-gene flanking regions of the mouse, rat, and human genes identified conserved sequence blocks containing binding sites for known gut transcription factors within the acinar cell-specific control region.
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U2 - 10.1074/jbc.M106264200
DO - 10.1074/jbc.M106264200
M3 - Article
C2 - 11562365
AN - SCOPUS:0035941216
SN - 0021-9258
VL - 276
SP - 44018
EP - 44026
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 47
ER -