Pan: a transcriptional regulator that binds chymotrypsin, insulin, and AP-4 enhancer motifs.
Two cDNAs were cloned that encode proteins (Pan-1 and Pan-2, with predicted molecular masses of 67.4 and 67.7 kD, respectively) that bind to a conserved transcriptional regulatory element present in pancreatic exocrine genes. The cDNAs are virtually identical in the region that encodes the amino-terminal 525 amino acids; they differ only by a 3-nucleotide insertion that results in the addition of a single amino acid. The cDNAs, however, code for related, but divergent, carboxy-terminal regions. Expression of the cloned cDNAs in HeLa cells activates expression of a cotransfected chimeric gene containing multimers of the pancreatic conserved element linked to a minimal promoter. Pan-1 and Pan-2 bind to the consensus sequence CAC/GCTGT/C, the CACCTGTC motif, which is present in transcriptional control elements of several genes. Both Pan-1 and Pan-2 bind to related motifs present in the rat insulin enhancer as well as a DNA segment containing the SV40 AP-4 element. The Pan-1 and Pan-2 cDNAs display extensive sequence identity with partial cDNA clones encoding E12 and E47, which bind to the immunoglobulin kappa E2 cis-active element, and may be derived from the same gene. These factors belong to a set of genetically distinct molecules, including AP-4 and MLTF, that bind to the CACCTGTC motif or related sequences. The Pan/E12,E47 proteins also show structural similarity with the Drosophila daughterless protein, MyoD, Myogenin, and Myf-5.
Hormone Research Institute, University of California, San Francisco 94143-0534.
C
C
Nelson
L P
LP
Shen
A
A
Meister
E
E
Fodor
W J
WJ
Rutter
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002918:Chymotrypsin / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D007328:Insulin / Q000235:genetics*; D008969:Molecular Sequence Data; D010179:Pancreas / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D015183:Restriction Mapping; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D007328:Insulin; D051820:TCF Transcription Factors; C553060:Tcf7l1 protein, rat; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; C055473:enhancer-binding protein AP-4; D004247:DNA; D002918:Chymotrypsin