Long-range function of an intergenic retrotransposon

Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):12992-7. doi: 10.1073/pnas.1004139107. Epub 2010 Jul 6.

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 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Pairing / genetics
  • Base Sequence
  • CCAAT-Binding Factor / metabolism
  • DNA, Intergenic / genetics*
  • Erythroid Precursor Cells / metabolism
  • GATA2 Transcription Factor / metabolism
  • Gene Expression Regulation
  • Genes, Switch
  • Genetic Loci / genetics
  • Globins / genetics
  • Humans
  • Integrases / metabolism
  • Mice
  • Mice, Transgenic
  • Models, Genetic
  • Molecular Sequence Data
  • RNA Polymerase II / metabolism
  • Recombination, Genetic / genetics
  • Retroelements / genetics*
  • Sequence Deletion / genetics
  • Terminal Repeat Sequences / genetics

Substances

  • CCAAT-Binding Factor
  • DNA, Intergenic
  • GATA2 Transcription Factor
  • Retroelements
  • Globins
  • Cre recombinase
  • Integrases
  • RNA Polymerase II