Long-range function of an intergenic retrotransposon

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 29; pp. 12992 - 12997
• Main Authors: Pi, Wenhu, Zhu, Xingguo, Wu, Min, Wang, Yongchao, Fulzele, Sadanand, Eroglu, Ali, Ling, Jianhua, Tuan, Dorothy, Goff, Stephen P.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 20.07.2010; National Acad Sciences
• Subjects: Animals; Base Pairing - genetics; Base Sequence; Biological Sciences; CCAAT-Binding Factor - metabolism; Deoxyribonucleic acid; DNA; DNA, Intergenic - genetics; Erythrocytes; Erythroid cells; Erythroid Precursor Cells - metabolism; GATA2 Transcription Factor - metabolism; Gene Expression Regulation; Genes; Genes, Switch; Genetic loci; Genetic Loci - genetics; Genomics; Globins - genetics; Humans; Integrases - metabolism; Intergenic DNA; Mice; Mice, Transgenic; Models, Genetic; Molecular Sequence Data; Promoter regions; Proteins; Recombination, Genetic - genetics; Retroelements - genetics; Retrotransposons; Retroviridae; RNA; RNA polymerase; RNA Polymerase II - metabolism; Sequence Deletion - genetics; Terminal Repeat Sequences - genetics; Transcription factors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1004139107

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.