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 language | English (US) |
|---|---|
| Pages (from-to) | 12992-12997 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 107 |
| Issue number | 29 |
| DOIs | |
| State | Published - Jul 20 2010 |
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Keywords
- BAC transgenic mice
- Globin gene switching
- NF-Y bound at CCAAT motif
- Transcriptional regulation
ASJC Scopus subject areas
- General
Cite this
Long-range function of an intergenic retrotransposon. / Pi, Wenhu; Zhu, Xingguo; Wu, Min; Wang, Yongchao; Fulzele, Sadanand T; Eroglu, Ali; Ling, Jianhua; Tuan Lo, Dorothy.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 29, 20.07.2010, p. 12992-12997.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Long-range function of an intergenic retrotransposon
AU - Pi, Wenhu
AU - Zhu, Xingguo
AU - Wu, Min
AU - Wang, Yongchao
AU - Fulzele, Sadanand T
AU - Eroglu, Ali
AU - Ling, Jianhua
AU - Tuan Lo, Dorothy
PY - 2010/7/20
Y1 - 2010/7/20
N2 - 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.
AB - 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.
KW - BAC transgenic mice
KW - Globin gene switching
KW - NF-Y bound at CCAAT motif
KW - Transcriptional regulation
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UR - http://www.scopus.com/inward/citedby.url?scp=77955627648&partnerID=8YFLogxK
U2 - 10.1073/pnas.1004139107
DO - 10.1073/pnas.1004139107
M3 - Article
VL - 107
SP - 12992
EP - 12997
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 29
ER -