A Long Terminal Repeat of the Human Endogenous Retrovirus ERV-9 Is Located in the 5′ Boundary Area of the Human β-Globin Locus Control Region

Long, Qiaoming; Bengra, Chikh; Li, Chunhua; Kutlar, Ferdane; Tuan, Dorothy

doi:10.1006/geno.1998.5608

Cited by 74 publications

(97 citation statements)

References 68 publications

(99 reference statements)

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“…The LTR RNAs did not appear to be read-through transcripts from neighboring DNAs, as synthesis of GFP mRNA initiated from the LTR enhancer was observed irrespective of the Tg integration sites in the four lines of Tg zebrafish. Moreover, earlier studies showed that ERV-9 LTRs, in the genome and in transfected plasmids, were active and initiated synthesis of LTR RNAs in multiple human cell types, including erythroid progenitor cells (5,6). The ERV-9 LTRs associated with different gene loci in the human genome appeared to exhibit tissue-specific enhancer activities in the adult progenitor cells.…”

Section: Discussionmentioning

confidence: 98%

“…In semiquantitative RT-PCR, the RNA was first reversibly transcribed with random hexamers into a cDNA master stock. Equal aliquots of the cDNA master stock were then separately amplified with different primer pairs under conditions in which the PCR ingredients were not exhausted so that the PCR products were within the linear range of PCR amplification (5,6). The respective forward and reverse primers of the seven primer pairs in the ␤-globin gene locus are as follows: (i) 4004-4029 and 4355-4380 (GenBank accession no.…”

Section: Methodsmentioning

confidence: 99%

“…Retrotransposons have been proposed to be selfish DNAs serving no host function (8). However, recent findings show that they contain regulatory sequences including enhancers and promoters (5,6,(9)(10)(11) and can serve relevant cellular function in modulating the transcription of cis-linked host genes.…”

mentioning

confidence: 99%

“…Transfection assays in human cell lines show that the ERV-9 LTRs from different human gene loci exhibit prominent enhancer activity in embryonic and hematopoietic cells (4)(5)(6).…”

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confidence: 99%

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The LTR enhancer of ERV-9 human endogenous retrovirus is active in oocytes and progenitor cells in transgenic zebrafish and humans

Yang

Wang

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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The solitary LTRs of ERV-9 human endogenous retrovirus are middle repetitive DNAs associated with 3,000 -4,000 human gene loci including the ␤-globin gene locus where the ERV-9 LTR is juxtaposed to the locus control region (␤-LCR) far upstream of the globin genes. The ERV-9 LTRs are conserved during primate evolution, but their function in the primate genomes is unknown. Here, we show that in transgenic zebrafish harboring the ␤-globin ERV-9 LTR coupled to the GFP gene, the LTR enhancer was active and initiated synthesis of GFP mRNA in oocytes but not in spermatozoa, and GFP expression in the embryos was maternally inherited. The LTR enhancer was active also in stem͞ progenitor cell regions of adult tissues of transgenic zebrafish. In human tissues, ERV-9 LTR enhancer was active also in oocytes and stem͞progenitor cells but not in spermatozoa and a number of differentiated, adult somatic cells. Transcriptional analyses of the human ␤-globin gene locus showed that the ␤-globin ERV-9 LTR enhancer initiated RNA synthesis from the LTR in the direction of the downstream ␤ locus control region and globin genes in ovary and erythroid progenitor cells. The findings suggest that, during oogenesis, ERV-9 LTR enhancers in the human genome could activate the cis-linked gene loci to synthesize maternal mRNAs required for early embryogenesis. Alternatively, the ERV-9 LTR enhancers, in initiating RNA syntheses into the downstream genomic DNAs, could transcriptionally potentiate and preset chromatin structure of the cis-linked gene loci in oocytes and adult stem͞progenitor cells.

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Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

“…Transfection assays in human cell lines show that the ERV-9 LTRs from different human gene loci exhibit prominent enhancer activity in embryonic and hematopoietic cells (4)(5)(6).…”

mentioning

confidence: 99%

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The LTR enhancer of ERV-9 human endogenous retrovirus is active in oocytes and progenitor cells in transgenic zebrafish and humans

Yang

Wang

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…We identified a putative brain-specific enhancer on the basis of conservation and of an enhancer-associated epigenetic signature; moreover this element exhibited cell-type-specific enhancer activity in reporter assays in ex vivo neural cells. Alternatively, both LTRs and SINEs have previously been demonstrated to exhibit enhancer functions in some contexts (Hambor et al 1993;Long et al 1998), so it is also possible that the repeat elements themselves may have gained an enhancer function. This has previously been observed at the human lipoprotein, Lp(a) locus (Wade et al 1997;Yang et al 1998).…”

Section: Gain Of Function In Gene Regulation and Chromosome Architecturementioning

confidence: 99%

Targeted deletion of a 170-kb cluster of LINE-1 repeats and implications for regional control

et al. 2018

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Approximately half the mammalian genome is composed of repetitive sequences, and accumulating evidence suggests that some may have an impact on genome function. Here, we characterized a large array class of repeats of long-interspersed elements (LINE-1). Although widely distributed in mammals, locations of such arrays are species specific. Using targeted deletion, we asked whether a 170-kb LINE-1 array located at a mouse imprinted domain might function as a modulator of local transcriptional control. The LINE-1 array is lamina associated in differentiated ES cells consistent with its AT-richness, and although imprinting occurs both proximally and distally to the array, active LINE-1 transcripts within the tract are biallelically expressed. Upon deletion of the array, no perturbation of imprinting was observed, and abnormal phenotypes were not detected in maternal or paternal heterozygous or homozygous mutant mice. The array does not shield nonimprinted genes in the vicinity from local imprinting control. Reduced neural expression of protein-coding genes observed upon paternal transmission of the deletion is likely due to the removal of a brain-specific enhancer embedded within the LINE array. Our findings suggest that presence of a 170-kb LINE-1 array reflects the tolerance of the site for repeat insertion rather than an important genomic function in normal development.

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A (GATA)7 motif located in the 5? boundary area of the human ?-globin locus control region exhibits silencer activity in erythroid cells

et al. 2000

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A 40-bp DNA, consisting of seven tandem GATA repeats, is located near the HS5 site in the 5' boundary area of the locus control region (LCR) of human beta-globin gene. This (GATA)(7) motif, named 5a, exhibits silencer activity in erythroid cells. In transfected, recombinant plasmids containing the chloramphenicol acetyltransferase (CAT) reporter gene, 5a repressed the activity of the cis-linked housekeeping phosphoglycerate kinase (pgk) promoter; 5a also repressed the activity of the cis-linked HS2 enhancer regardless of whether the CAT gene was driven by the pgk or the epsilon-globin promoter. Repression by 5a was most severe when 5a was spliced upstream of HS2 at a distance of less than 200 bases from the HS2 enhancer core. The silencer activity of 5a was independent of whether the component GATA motifs were in head to tail orientation as in the wild type 5a or in head to head or tail to tail orientation as in a mutant 5a. Band shift experiments show that the GATA-1 protein binds to both 5a and the mutant 5a and forms a large protein complex. Together, the results suggest that GATA-1 bound at 5a is a strong, proximal repressor of HS2 enhancer activity.

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A Long Terminal Repeat of the Human Endogenous Retrovirus ERV-9 Is Located in the 5′ Boundary Area of the Human β-Globin Locus Control Region

Cited by 74 publications

References 68 publications

The LTR enhancer of ERV-9 human endogenous retrovirus is active in oocytes and progenitor cells in transgenic zebrafish and humans

The LTR enhancer of ERV-9 human endogenous retrovirus is active in oocytes and progenitor cells in transgenic zebrafish and humans

Targeted deletion of a 170-kb cluster of LINE-1 repeats and implications for regional control

A (GATA)7 motif located in the 5? boundary area of the human ?-globin locus control region exhibits silencer activity in erythroid cells

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