title: Long non-coding RNAs transcribed by ERV-9 LTR retrotransposon act in cis to modulate long-range LTR enhancer function.
abstract: LTR retrotransposons are repetitive DNA elements comprising ∼10% of the human genome. However, LTR sequences are disproportionately present in human long, non-coding RNAs (lncRNAs). Whether and how the LTR lncRNAs serve biological functions are largely unknown. Here we show that in primary human erythroblasts, lncRNAs transcribed from the LTR retrotransposons of ERV-9 human endogenous retrovirus activated transcription of key erythroid genes and modulated ex vivo erythropoiesis. To dissect the functional mechanism of ERV-9 lncRNAs, we performed genome-wide RNA and ChIRP analyses before and after global knockdown or locus-specific deletion of ERV-9 lncRNAs in human erythroblasts carrying ∼4000 copies of the ERV-9 LTRs and in transgenic mouse erythroblasts carrying a single copy of the primate-specific ERV-9 LTR in the 100 kb human β-globin gene locus. We found that ERV-9 lncRNAs acted in cis to stabilize assembly of the ERV-9 LTR enhancer complex and facilitate long-range LTR enhancer function in activating transcription of downstream, cis-linked globin genes. Our findings suggested that LTR lncRNAs transcribed from many of the 4000 copies of ERV-9 LTR retrotransposons acted by a similar cis mechanism to modulate LTR enhancer function in activating transcription of downstream genes critical to cellular processes including erythropoiesis.
authors.affiliation: Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USA.
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Hu
authors.affiliation: Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USA.
authors.forename: Wenhu
authors.initials: W
authors.lastname: Pi
authors.affiliation: Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USA.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Cancer Center, Augusta University, Augusta, GA 30912, USA.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USA.
authors.forename: Hongseok
authors.initials: H
authors.lastname: Ha
authors.affiliation: Cancer Center, Augusta University, Augusta, GA 30912, USA.
authors.forename: Huidong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Biostatics and Epidemiology, Augusta University, Augusta, GA 30912, USA.
authors.forename: Jeong-Hyeon
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USA.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Tuan
mesh_terms: D000818:Animals; D001483:Base Sequence; D020077:Endogenous Retroviruses / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis; D056426:Genetic Loci; D016678:Genome; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D061251:Primary Cell Culture; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D018626:Retroelements; D020079:Terminal Repeat Sequences; D014158:Transcription, Genetic; D055544:beta-Globins / Q000235:genetics* / Q000378:metabolism
chemical_list: D062085:RNA, Long Noncoding; D018626:Retroelements; D055544:beta-Globins