Genomic organization and characterization of promoter function of the human CDK9 gene

CDK9 is the catalytic subunit of a general RNA polymerase II (RNAP II) elon gation factor termed p-TEFb which is targeted by the human immunodeficiency virus (HIV) Tat protein to activate elongation of the integrated proviral genome. CDK9 mRNA and protein levels have been observed to be induced in ac tivated peripheral blood lymphocytes, a cell type relevant to HIV infection . To investigate mechanisms that regulate CDK9 RNA expression, we isolated genomic sequences containing the human CDK9 gene and found that CDK9 coding sequences are interrupted by six introns. There is a major transcriptional start site located 79 nucleotides upstream of the ATG initiator codon at n ucleotide +1. Nucleotides -352 to -1 contain all the transcriptional regula tory elements needed for full promoter activity in transient expression ass ays. The CDK9 promoter contains features characteristic of a housekeeping g ene, including GC-rich sequences and absence of a functional TATA element. The CDK9 promoter possesses high constitutive activity and may therefore ha ve utility in expression vectors or gene therapy vectors. (C) 2000 Elsevier Science B.V. All rights reserved.