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Molecular and Cellular Biology, April 2005, p. 3276-3285, Vol. 25, No. 8
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.8.3276-3285.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Strong Polyadenylation and Weak Pausing Combine To Cause Efficient Termination of Transcription in the Human ^G-Globin Gene

Kathryn E. Plant, Michael J. Dye, Celina Lafaille, and Nick J. Proudfoot^*

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

Received 17 September 2004/ Returned for modification 18 October 2004/ Accepted 23 December 2004

The human -globin genes form part of a 5-kb tandem duplication within the ß-globin gene cluster on chromosome 11. Despite a high degree of identity between the two genes, we show that while the upstream ^G-globin gene terminates transcription efficiently, termination in the ^A gene is inefficient. This is primarily due to the different strengths of the poly(A) signals of the two genes; ^G-globin has a functionally stronger poly(A) signal than the ^A gene. The probable cause of this difference in poly(A) efficiency characteristics lies with a number of base changes which reduce the G/U content of the GU/U-rich region of the ^A poly(A) signal relative to that of ^G. The 3' flanking regions of the two -globin genes have similar abilities to promote transcription termination. We found no evidence to suggest a cotranscriptional cleavage event, such as that seen in the human ß-globin gene, occurs in either -globin 3' flank. Instead we find evidence that the 3' flank of the ^G-globin gene contains multiple weak pause elements which, combined with the strong poly(A) signal the gene possesses, are likely to cause gradual termination across the 3' flank.

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* Corresponding author. Mailing address: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom. Phone: 01865 275566. Fax: 01865 275556. E-mail: nicholas.proudfoot{at}pathology.oxford.ac.uk.

Present address: School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom.

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Molecular and Cellular Biology, April 2005, p. 3276-3285, Vol. 25, No. 8
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.8.3276-3285.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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