The Cloned Promoter of the Human DNA β-Polymerase Gene Contains a cAMP Response Element Functional in HeLa Cells

The mammalian DNA β-polymerase (β-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 β-pol promoter fusion genes, the cloned human β-pol promoter is transcriptionally regulated by signals acting through the single palindromic sequence (GTGACGTCAC) 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 β-pol promoter; activation also can be observed by coexpression of the protein kinase A catalytic subunit. Experiments with mutagenized β-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.