The cloned promoter of the human DNA beta-polymerase gene contains a cAMP response element functional in HeLa cells.
The mammalian DNA beta-polymerase (beta-pol) gene is constitutively expressed in cultured cells as a function of growth stage and DNA replication, but is expressed in rodents in a tissue-specific fashion. As revealed by transient expression experiments with wild-type and mutated beta-pol promoter fusion genes, the cloned human beta-pol promoter is transcriptionally regulated by signals acting through the single palindromic sequence (GT-GACGTCAC) known as an ATF/CRE-binding site centered at position -45 in the core promoter. Although the mere presence of the ATF/CRE palindromic sequence in a promoter does not always confer cAMP responsiveness or protein binding over and around the ATF/CRE sequence, we find that agents that increase cAMP levels (forskolin and IBMX) in HeLa cells activate the beta-pol promoter; activation also can be observed by coexpression of the protein kinase A catalytic subunit. Experiments with mutagenized beta-pol promoters indicate that the ATF/CRE-binding site mediates these effects. Thus, the ATF/CRE-binding site in the context of this TATA-less constitutive promoter is able to respond to the kinase A signal transduction pathway.
Englander
E W
EW
Laboratory of Biochemistry, National Cancer Institute, Bethesda, MD 20892.
Wilson
S H
SH
D001483:Base Sequence; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein; D004256:DNA Polymerase I / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006367:HeLa Cells / Q000201:enzymology* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D000242:Cyclic AMP; D011494:Protein Kinases; D004256:DNA Polymerase I