This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Whitelaw, E Articles by Proudfoot, N J Search for Related Content PubMed PubMed Citation Articles by Whitelaw, E Articles by Proudfoot, N J

Transcriptional promiscuity of the human alpha-globin gene.

Sir William Dunn School of Pathology, University of Oxford, United Kingdom.

ABSTRACT

The human alpha-globin gene displays the unusual property of transcriptional promiscuity: that is, it functions in the absence of an enhancer when transfected into nonerythroid cell lines. It is also unusual in that its promoter region lies in a hypomethylated HpaII tiny fragment (HTF) island containing multiple copies of the consensus sequence for the SP1-binding site. We have investigated whether there is a relationship between these two observations. First, we investigated the mouse alpha-globin gene since it does not lie in an HTF island. We have demonstrated that it was not transcriptionally promiscuous. Second, we studied the transcriptional activity of the human alpha-globin gene in the absence of the GC-rich region containing putative SP1-binding sites and found a small (two- to threefold) but consistent positive effect of this region on transcriptional activity in both nonerythroid and erythroid cell lines. However, this effect did not account for the promiscuous nature of the human alpha-globin gene. We found that in a nonreplicating system, the human alpha-globin gene, like that of the mouse, required a simian virus 40 enhancer in order to be transcriptionally active in nonerythroid and erythroid cell lines. Since we only observed enhancer independence of the human alpha-globin gene in a high-copy-number replicating system, we suggest that competition for trans-acting factors could explain these results. Finally, our experiments with the erythroid cell line Putko suggest that there are no tissue-specific enhancers within 1 kilobase 5' of the human alpha-globin cap site or within the gene itself.

This article has been cited by other articles:

• Zong, Y., Zhou, S., Fatima, S., Sorrentino, B. P. (2006). Expression of Mouse Abcg2 mRNA during Hematopoiesis Is Regulated by Alternative Use of Multiple Leader Exons and Promoters. J. Biol. Chem. 281: 29625-29632 [Abstract] [Full Text]  
• James-Pederson, M., Yost, S., Shewchuk, B., Zeigler, T., Miller, R., Hardison, R. (1995). Flanking and Intragenic Sequences Regulating the Expression of the Rabbit alpha-Globin Gene. J. Biol. Chem. 270: 3965-3973 [Abstract] [Full Text]  
• Weichs an der Glon, C, Monks, J, Proudfoot, N J (1991). Occlusion of the HIV poly(A) site.. Genes Dev. 5: 244-253 [Abstract]  
• Campbell, P L, Kulozik, A E, Woodham, J P, Jones, R W (1990). Induction by HMBA and DMSO of genes introduced into mouse erythroleukemia and other cell lines by transient transfection.. Genes Dev. 4: 1252-1266 [Abstract]  
• Hanscombe, O, Vidal, M, Kaeda, J, Luzzatto, L, Greaves, D R, Grosveld, F (1989). High-level, erythroid-specific expression of the human alpha-globin gene in transgenic mice and the production of human hemoglobin in murine erythrocytes.. Genes Dev. 3: 1572-1581 [Abstract]