Pan: a transcriptional regulator that binds chymotrypsin, insulin, and AP-4 enhancer motifs

• Published in: Genes & development 1990-06, Vol.4 (6), p.1035-1043
• Main Authors: Nelson, C, Shen, L P, Meister, A, Fodor, E, Rutter, W J
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Blotting, Southern; Chymotrypsin - genetics; DNA - genetics; DNA - isolation & purification; DNA-Binding Proteins - genetics; Enhancer Elements, Genetic; enhancers; Gene Expression Regulation; genes; Insulin - genetics; Molecular Sequence Data; pancreas; Pancreas - metabolism; Promoter Regions, Genetic; Rats; Restriction Mapping; TCF Transcription Factors; Transcription Factor 7-Like 1 Protein; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.4.6.1035

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.