Multiple Promoter Elements Interact to Control the Transcription of the Potassium Channel Gene, KCNJ2

Potassium channels play important roles in shaping the electrical properties of excitable cells. Toward understanding the transcriptional regulation of a member of the inwardly rectifying potassium channel family, we have characterized the genomic structure and 5'-proximal promoter of the murine Kcnj2 gene (also referred to as IRK1 and Kir2.1). The Kcnj2 transcription unit is composed of two exons separated by a 5.5-kilobase pair intron. Deletion analysis of 5'-flanking sequences identified a promiscuously active 172-base pair minimal promoter, whereas expression from a construct containing additional upstream sequences was cell type-restricted. The minimal promoter contained an E box, a Y box, and three GC box consensus elements but lacked both TATA and CCAAT box elements. The activity of the minimal promoter was found to be controlled by a combination of the activities of the transcription factors Sp1, Sp3, and NF-Y. The interplay between Sp1, Sp3, and NF-Y within the architecture of the Kcnj2 promoter, the ubiquitous nature of these trans-acting factors, and the action of tissue-selective repressor element(s) may combine to enable a wide variety of cell types to differentially regulate Kcnj2 expression through transcriptional control.