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

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.

ACKNOWLEDGMENTS

We thank the members of the lab of N.J.P. for advice during these studies.

This work was supported by the Wellcome Trust (program grant to N.J.P.).