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Long-range function of an intergenic retrotransposon

Source: Proc. Natl. Acad. Sci. U.S.A. 107, 12992 (2010);

Issue Date: 1 August 2010

PUBLICATION DATA
ISSN:
1553-9628 (online)
Publisher:
AIP is a member of CrossRef NAS
Wenhu Pi
Departments of Biochemistry and Molecular Biology and Orthopedic Surgery and Institute of Molecular Medicine and Genetics, School of Medicine, Medical College of Georgia, Augusta, GA 30912

Xingguo Zhu


Min Wu


Yongchao Wang


Sadanand Fulzele


Ali Eroglu


Jianhua Ling


Dorothy Tuan

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 gamma- and adult beta-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. ©2010 National Academy of Sciences

(As supplied by publisher.)

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