An E-box element localized in the first intron mediates regulation of the prothymosin alpha gene by c-myc.
In RAT1A fibroblasts, expression of the prothymosin alpha gene is under the transcriptional control of the c-myc proto-oncogene. We have now cloned the rat gene encoding prothymosin alpha and show that the cloned gene is regulated by c-myc in vivo. We find that regulation by c-myc is mediated by sequences downstream of the transcriptional start site, whereas the promoter is constitutive and not regulated by c-myc. We have identified an enhancer element within the first intron that is sufficient to mediate a response to Myc and Max in transient transfection assays and to activation of estrogen receptor-Myc chimeras in vivo. We find that this element contains a consensus Myc-binding site (CACGTG). Disruption of this site abolishes the response to Myc and Max in both transient and stable assays. Mutants of either Myc or Max that are deficient for heterodimerization fail to regulate the prothymosin alpha gene, suggesting that a heterodimer between Myc and Max activates the prothymosin alpha gene. Our data define the prothymosin alpha gene as a bona fide target gene for c-myc.
Gaubatz
S
S
Zentrum für Molekulare Biologie Heidelberg, Federal Republic of Germany.
Meichle
A
A
Eilers
M
M
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D003001:Cloning, Molecular; D016384:Consensus Sequence; D006224:Cricetinae; D004247:DNA / Q000032:analysis; D017931:DNA Primers; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D016259:Genes, myc; D015698:Genomic Library; D006801:Humans; D007438:Introns; D007700:Kinetics; D008156:Luciferases / Q000096:biosynthesis / Q000378:metabolism; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D000090063:Proto-Oncogene Mas; D051381:Rats; D011916:Rats, Inbred F344; D012689:Sequence Homology, Nucleic Acid; D013947:Thymosin / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
D017931:DNA Primers; C000715470:MAS1 protein, human; D011498:Protein Precursors; D000090063:Proto-Oncogene Mas; C040782:prothymosin alpha; D013947:Thymosin; D004247:DNA; D008156:Luciferases