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