Trans-activation of human globin genes by HTLV-I tax1.

Important note: Information in this article was accurate in 1990. The state of the art may have changed since the publication date.

Trans-activation of human globin genes by HTLV-I tax1.

Blood. 1989 Dec;74(8):2749-54. Unique Identifier : AIDSLINE MED/90057689
Fox HB; Gutman PD; Dave HP; Cao SX; Mittelman M; Berg PE; Schechter AN; Laboratory of Chemical Biology, National Institute of Diabetes,; Digestive and Kidney Diseases, Bethesda, MD 20892.

Abstract: We studied the effects of a known retroviral trans-activating factor, HTLV-I tax1, on transcription of human globin genes. Transfection of HeLa cells by the cloned tax1 gene stimulated activity of both the beta- and epsilon-globin promoters approximately 20-fold, as measured by chloramphenicol acetyl transferase (CAT) assays. Studies of promoter 5'-deletion mutants revealed that the trans-activation response required only 185 base pairs (bp) of beta-globin 5'-flanking sequence or 177 bp of epsilon-globin 5' flanking sequence. These promoter regions contain either two (for beta) or three (for epsilon) copies of the pentanucleotide sequence CTGAC, which is characteristic of previously described tax1-responsive promoters. We also stably transfected tax1 into the erythroid cell line K562. Transfectants expressing tax1 showed increased transcription of epsilon-, gamma-, zeta-, and alpha-globins. This indicates that tax1 can stimulate transcription of globin genes in their native chromosomal location. This was confirmed by measurements of increases in intracellular hemoglobin as determined by an increased percentage of cells staining with benzidine and by spectrophotometric measurements of hemoglobin. The observed trans-activation of globin genes by tax1 may provide insight into normal regulation of globin genes by clarifying cis regulatory sequences. Furthermore, it suggests that the trans-acting effects of tax1 on heterologous genes are more widespread than was previously appreciated.

Keywords: Base Sequence DNA Mutational Analysis Gene Expression Regulation Globin/*GENETICS Hela Cells Human HTLV-I/*GENETICS Molecular Sequence Data *Promoter Regions (Genetics) Recombinant Fusion Proteins/GENETICS *Regulatory Sequences, Nucleic Acid Trans-Activators/*PHYSIOLOGY Transcription, Genetic JOURNAL ARTICLE
900330
M9030672

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