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

H. B. Fox, P. D. Gutman, H. P.G. Dave, S. X. Cao, M. Mittelman, P. E. Berg, A. N. Schechter

Research output: Contribution to journalArticlepeer-review

Abstract

We studied the effect 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 β- and ε-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 β-globin 5'-flanking sequence or 177 bp of ε-globin 5' flanking sequence. These promoter regions contain either two (for β) or three (for ε) 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 ε-, γ-, ξ-, and α-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 suggest that the trans-acting effects of tax1 on heterologous genes are more widespread than was previously appreciated.

Original languageEnglish
Pages (from-to)2749-2754
Number of pages6
JournalBlood
Volume74
Issue number8
DOIs
StatePublished - 1989
Externally publishedYes

Fingerprint

Dive into the research topics of 'Trans-activation of human globin genes by HTLV-I tax1'. Together they form a unique fingerprint.

Cite this