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 journalArticle

48 Citations (Scopus)

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

Fingerprint

Retroelements
Terminal Repeat Sequences
Endogenous Retroviruses
Globins
Genes
Erythroid Cells
Intergenic DNA
RNA Polymerase II
Human Genome
Transcription Factors
RNA
DNA

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 journalArticle

Pi, Wenhu ; Zhu, Xingguo ; Wu, Min ; Wang, Yongchao ; Fulzele, Sadanand T ; Eroglu, Ali ; Ling, Jianhua ; Tuan Lo, Dorothy. / Long-range function of an intergenic retrotransposon. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 29. pp. 12992-12997.
@article{79be59f65f414f7885126df08c166733,
title = "Long-range function of an intergenic retrotransposon",
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.",
keywords = "BAC transgenic mice, Globin gene switching, NF-Y bound at CCAAT motif, Transcriptional regulation",
author = "Wenhu Pi and Xingguo Zhu and Min Wu and Yongchao Wang and Fulzele, {Sadanand T} and Ali Eroglu and Jianhua Ling and {Tuan Lo}, Dorothy",
year = "2010",
month = "7",
day = "20",
doi = "10.1073/pnas.1004139107",
language = "English (US)",
volume = "107",
pages = "12992--12997",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "29",

}

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

UR - http://www.scopus.com/inward/record.url?scp=77955627648&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955627648&partnerID=8YFLogxK

U2 - 10.1073/pnas.1004139107

DO - 10.1073/pnas.1004139107

M3 - Article

C2 - 20615953

AN - SCOPUS:77955627648

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 -