The catalytic subunit α′ gene of human protein kinase CK2 (CSNK2A2):: Genomic organization, promoter identification and determination of Ets1 as a key regulator

The human genome contains four protein kinase CK2 loci, enclosing three active genes coding for the catalytic subunits alpha and alpha' and the regulatory subunit beta, and a processed alpha subunit pseudogene. Extensive structure and transcriptional control data of the genes are available, except for the CK2 alpha' gene (CSNK2A2). Using in silico and experimental approaches, we find CSNK2A2 to be located on the long arm of chromosome 16 (in contrast to published data), to span 40 kb and to consist of 12 exons, with the translational start in Exon 1 and the stop in Exon 11. Exon/intron boundaries conform to the gt/ag rule, and various potential polyadenylation signals determine transcript species with lengths of 1.7-5.7 kb. The upstream region of the gene displays housekeeping characteristics, lacking a TATA box and possessing several GC boxes as well as a CpG island around Exon 1. According to reporter gene assay results, the promoter activity ranges from -1308 to 197 with the highest activity in region -396 to -129. This region contains binding motifs for various transcription factors, including NF kappa B, Sp and Ets family members. Site-directed mutagenesis indicates that the Ets motifs play, in cooperation with Sp motif clusters, a central role in regulating CK2 alpha' gene transcription. A similar control has been described for the transcription of the CK2 alpha and CK2 beta genes so that the presented data are compatible with the assumption of a coordinate transcriptional regulation of all three active human CK2 genes decisively determined by Ets family members.