Long-range function of an intergenic retrotransposon

Wenhu Pi, Xingguo Zhu, Min Wu, Yongchao Wang, Sadanand T Fulzele, Ali Eroglu, Jianhua Ling, Dorothy Tuan Lo

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)12992-12997
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number29
DOIs
StatePublished - Jul 20 2010

Keywords

  • BAC transgenic mice
  • Globin gene switching
  • NF-Y bound at CCAAT motif
  • Transcriptional regulation

ASJC Scopus subject areas

  • General

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