Large conductance, calcium-activated potassium (maxiK) channels are expressed in 
nerve, muscle, and other cell types and are important determinants of smooth 
muscle tone. To determine the mechanisms involved in the transcriptional 
regulation of maxiK channels, we characterized the promoter regions of the pore 
forming (alpha) and regulatory (beta) subunits of the human channel complex. 
Maximum promoter activity (up to 12.3-fold over control) occurred between 
nucleotides -567 and -220 for the alpha subunit (hSlo) gene. The minimal 
promoter is GC-rich with 5 Sp-1 binding sites and several TCC repeats. Other 
transcription factor-binding motifs, including c/EBP, NF-kB, PU.1, PEA-3, Myo-D, 
and E2A, were observed in the 5'-flanking sequence. Additionally, a CCTCCC 
sequence, which increases the transcriptional activity of the SM1/2 gene in 
smooth muscle, is located 27 bp upstream of the TATA-like sequence, a location 
identical to that found in the SM1/2 5'-flanking region. However, the promoter 
directed equivalent expression when transfected into smooth muscle and other 
cell types. Analysis of the hSlo beta subunit 5'-flanking region revealed a TATA 
box at position -77 and maximum promoter activity (up to 11.0-fold) in a 200 bp 
region upstream from the cap site. Binding sites for GATA-1, Myo-D, c-myb, 
Ets-1/Elk-1, Ap-1, and Ik-2 were identified within this sequence. Two CCTCCC 
elements are present in the hSlo beta subunit promoter, but tissue-specific 
transcriptional activity was not observed. The lack of tissue-specific promoter 
activity, particularly the finding of promoter activity in cells from tissues in 
which the maxiK gene is not expressed, suggests a complex channel regulatory 
mechanism for hSlo genes. Moreover, the lack of similarity of the promoters of 
the two genes suggests that regulation of coordinate expression of the subunits 
does not occur through equivalent cis-acting sequences.