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

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Abstract
The human γ-globin genes form part of a 5-kb tandem duplication within the β-globin gene cluster on chromosome 11. Despite a high degree of identity between the two genes, we show that while the upstream Gγ-globin gene terminates transcription efficiently, termination in the Aγ gene is inefficient. This is primarily due to the different strengths of the poly(A) signals of the two genes; Gγ-globin has a functionally stronger poly(A) signal than the Aγ 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 Aγ poly(A) signal relative to that of Gγ. The 3′ flanking regions of the two γ-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 β-globin gene, occurs in either γ-globin 3′ flank. Instead we find evidence that the 3′ flank of the Gγ-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.