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Edited by Stephen P. Goff, Columbia University College of Physicians and Surgeons, New York, NY, and approved June 8, 2010 (received for review March 29, 2010)
Abstract
Retrotransposons including endogenous retroviruses and their solitary long terminal repeats (LTRs) compose >40% of the human genome. Many of them are located in intergenic regions far from genes. Whether these intergenic retrotransposons serve beneficial host functions is not known. Here we show that an LTR retrotransposon of ERV-9 human endogenous retrovirus located 40–70 kb upstream of the human fetal γ- and adult β-globin genes serves a long-range, host function. The ERV-9 LTR contains multiple CCAAT and GATA motifs and competitively recruits a high concentration of NF-Y and GATA-2 present in low abundance in adult erythroid cells to assemble an LTR/RNA polymerase II complex. The LTR complex transcribes intergenic RNAs unidirectionally through the intervening DNA to loop with and modulate transcription factor occupancies at the far downstream globin promoters, thereby modulating globin gene switching by a competitive mechanism.
Footnotes
- 3To whom correspondence should be addressed. dtuanlo{at}mcg.edu.
Author contributions: W.P., X.Z., J.L., and D.T. designed research; W.P., X.Z., M.W., and Y.W. performed research; W.P., X.Z., J.L., and D.T. analyzed data; S.F. and A.E. contributed new reagents/analytic tools; and D.T. wrote the paper.
This article is a PNAS Direct Submission.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1004139107/-/DCSupplemental.
Long-range function of an intergenic retrotransposon
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