Abstract
The sequence 5′ TTGGPyCAAT 3′ (the ‘CCAAT box’) is a constituent of the promoter region of many eukaryotic and prokaryotic genes1,2 and is believed to play a part in promoter function3,4. A characteristic of the two fetal human globin genes (Aγ and Gγ) is a duplication of a 12-base pair (bp) sequence containing the CCAAT box. Here we report a G → A substitution in the TTG sequence of the distal CCAAT box of the Aγ-globin gene in an individual with the Aγ (Greek) type of hereditary persistence of fetal haemoglobin (HPFH). This represents the first report of a natural mutation of the CCAAT box in a eukaryotic gene. The fact that this transition is associated with inappropriate expression of the Aγ gene in adult life suggests that the CCAAT box (or its surrounding sequences) may have a role in the developmental control of γ-globin genes.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Benoist, C., O'Hare, K., Breathnach, R. & Chambon, P. Nucleic Acids Res. 8, 127–142 (1980).
Gilbert, W. in RNA Polymerase (eds Losick, R. & Chamberlain, M.) 193–205 (Cold Spring Harbor Laboratory, New York, 1979).
Dierks, P. et al. Cell 32, 695–706 (1983).
Grosveld, G. C., Rosenthal, A. & Flavell, R. Nucleic Acids Res. 10, 4951–4972 (1982).
Maniatis, T., Fritsch, E. F., Lauer, J. & Lawn, R. M. A. Rev. Genet. 14, 145–178 (1980).
Efstratiadis, A. et al. Cell 21, 653–668 (1980).
Weatherall, D. J. & Clegg, J. B. The Thalassaemia Syndromes 2nd edn (Blackwell Scientific, Oxford, 1972).
Fritsch, E., Lawn, R. & Maniatis, T. Nature 279, 598–603 (1979).
Tuan, D., Murnane, M., DeRiel, J. & Forget, B. Nature 258, 335–337 (1980).
Bernards, R. & Flavell, R. A. Nucleic Acids Res. 8, 1521–1534 (1980).
Fessas, P. & Stamatoyannopoulos, G. Blood 24, 223–240 (1964).
Huisman, T., Schroeder, W. & Stamatoyannopoulos, G. J. clin. Invest. 49, 1035–1040 (1970).
Sofroniadou, K., Wood, W., Nute, P. & Stamatoyannopoulos, G. Br. J. Haemat. 29, 137–148 (1975).
Clegg, J. B. et al. Br. J. Haemat. 43, 521–536 (1979).
Papayannopoulou, Th., Lawn, R. M., Stamatoyannopoulos, G. & Maniatis, T. Br. J. Haemat. 50, 387–399 (1982).
Farquhar, M. et al., Am. J. hum. Genet. 35, 611–620 (1983).
Moschonas, N., de Boer, E. & Flavell, R. A. Nucleic Acids Res. 10, 2109–2120 (1982).
Kohen, G., Philippe, N. & Godet, J. Hum. Genet. 62, 121–123 (1982).
Van der Ploeg, L. et al. Nature 283, 637–642 (1980).
Slightom, J., Blechl, A. & Smithies, O. Cell 21, 627–638 (1980).
Shen, S., Slightom, J. & Smithies, O. Cell 26, 191–203 (1981).
Collins, F. et al. Nature 313, 325–326 (1985).
Collins, F., Stoeckert, C., Serjeant, G., Forget, B. & Weissman, S. Proc. natn. Acad. Sci. U.S.A. 81, 4894–4898 (1984).
Giglioni, B. et al. EMBO J. 3, 2641–2645 (1984).
Siebenlist, U., Simpson, R. & Gilbert, W. Cell 20, 269–281 (1980).
Southern, E. J. molec. Biol. 98, 503–517 (1975).
Lawn, F., Fritsch, E., Parker, R., Blake, G. & Maniatis, T. Cell 15, 1157–1174 (1978).
Lawn, R., Efstratiadis, A., O'Connell, C. & Maniatis, T. Cell 21, 647–651 (1980).
Blin, N. & Stafford, D. W. Nucleic Acids Res. 3, 2303–2308 (1976).
Shafit-Azgardo, B., Maio, J. & Brown, F. Nucleic Acids Res. 10, 3175–3193 (1982).
Hohn, B. & Collins, J. Gene 11, 291–298 (1980).
Ish-Horowicz, D. & Burke, J. Nucleic Acids Res. 9, 2989–2998 (1981).
Grosveld, F. G., Dahl, H., deBoer, E. & Flavell, R. Gene 13, 227–237 (1981).
Barsh, G., Seeburg, P. & Gelinas, R. Nucleic Acids Res. 11, 3939–3958 (1983).
Norrander, J., Kempe, T. & Messing, J. Gene 26, 101–106 (1983).
Henikoff, S. Gene 28, 351–359 (1984).
Sanger, F., Nicklen, S. & Coulson, A. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gelinas, R., Endlich, B., Pfeiffer, C. et al. G to A substitution in the distal CCAAT box of the Aγ-globin gene in Greek hereditary persistence of fetal haemoglobin. Nature 313, 323–325 (1985). https://doi.org/10.1038/313323a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/313323a0
This article is cited by
-
Episomal vectors based on S/MAR and the β-globin Replicator, encoding a synthetic transcriptional activator, mediate efficient γ-globin activation in haematopoietic cells
Scientific Reports (2019)
-
The Hellenic type of nondeletional hereditary persistence of fetal hemoglobin results from a novel mutation (g.-109G>T) in the HBG2 gene promoter
Annals of Hematology (2009)
-
SUMO-conjugating enzyme (Sce) and FK506-binding protein (FKBP) encoding rice (Oryza sativa L.) genes: genome-wide analysis, expression studies and evidence for their involvement in abiotic stress response
Molecular Genetics and Genomics (2008)
-
The Nuclear Factor Y subunits NF-YB2 and NF-YB3 play additive roles in the promotion of flowering by inductive long-day photoperiods in Arabidopsis
Planta (2008)
-
Identification, characterization and expression analysis of transcription factor (CBF) genes in rice (Oryza sativa L.)
Frontiers of Agriculture in China (2008)
