Isolation and characterization of the human cyclin T1 promoter

Cyclin T1 (CycT1) is a regulatory subunit of a general RNA polymerase II (R NAP II) elongation factor termed P-TEFb. The human immunodeficiency virus T at protein directly associates with CycT1 to utilize CycT1/P-TEFb (also cal led TAK) for activation of RNAP II elongation of the integrated proviral ge nome. CycT1 mRNA and protein levels are induced in activated human peripher al blood lymphocytes and CycT1 protein levels are induced by a post-transcr iptional mechanism when human U937 promonocytic cells are stimulated to dif ferentiate into macrophage-like cells. To investigate mechanisms that regul ate CycT1 RNA expression, we isolated the CycT1 promoter. Multiple transcri ption start sites were identified within 330 nucleotides upstream of the AT G initiation codon at +1. The CycT1 promoter lacks a TATA element and posse sses high constitutive activity in plasmid transfection assays. Two distinc t regions of the promoter were identified upstream of +1 that contain criti cal regulatory elements for CycT1 promoter function. (C) 2000 Elsevier Scie nce B.V. All rights reserved.