Structure and expression of mouse VL30 genes.

Hodgson, Clague P.; Elder, Paula K.; Ono, Tetsuya; Foster, Douglas N.; Getz, Michael J.

doi:10.1128/mcb.3.12.2221

Cited by 58 publications

(32 citation statements)

References 39 publications

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“…Furthermore, a duplication of four nucleotides of host DNA at the integration site, and the fact that 2 bp are missing from the end of each LTR, suggests that the integration of VL30 into the agouti gene occurred through the same mechanism that is normally associated with the integration of retroviral sequences (Dhar et al 1980;Shimotohno et al 1980;Van Buren et al 1980;Varmus 1982). This finding is in accord with VL30 integrations that have been characterized previously (Hodgson et al 1983;Itin and Keshet 1983).…”

supporting

confidence: 82%

Molecular analysis of reverse mutations from nonagouti (a) to black-and-tan (a(t)) and white-bellied agouti (Aw) reveals alternative forms of agouti transcripts.

Bultman¹,

Klebig²,

Michaud³

et al. 1994

Genes Dev.

109

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The agouti gene regulates the differential production of eumelanin (black or brown) and phaeomelanin (yellow) pigment granules by melanocytes in the hair follicles of mice. The original nonagouti [a] allele, which confers a predominantly black coat color, has been shown to revert to two other more dominant agouti alleles, black-and-tan {a*) and white-bellied agouti (A**^, with an exceptionally high frequency. The a' and A^ alleles confer phenotypes in which the pigmentation is not uniformly distributed over the dorsal and ventral surfaces of the animal; in both cases the ventral surface of the animal is markedly lighter than the dorsal surface due to an increase in phaeomelanin production. To understand the unusually high reversion rate of a to a' or A^, and to decipher the molecular events associated with the different pigmentation patterns associated with these three agouti alleles, we have characterized a, a* and A^ at the molecular level. Here, we report that insertions of 11, 6, and 0.6 kb are present at precisely the same position in the first intron of the agouti gene in a, fl', and A^, respectively. The a insertion consists of a 5.5-kb VL30 element that has incorporated 5.5 kb of additional sequence internally; this internal sequence is flanked by 526-bp direct repeats. The a* allele contains only the VL30 element and a single, internal 526-bp repeat. The A^ allele has only a solo VL30 LTR. Based on the comparison of the structure of the a* and A^ insertions, we propose that reverse mutations occur by excision of inserted sequences in a through homologous recombination, utilizing either the 526-bp direct repeats to generate a* or the VL30 LTRs to generate A^. Moreover, the analysis of these three alleles has allowed us to identify additional exons of the agouti gene that give rise to alternatively processed forms of agouti mRNA. We demonstrate that the distinct insertions in a, a* and A^ cause pigmentation differences by selectively inactivating the expression of different forms of agouti transcripts.

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supporting

confidence: 82%

Molecular analysis of reverse mutations from nonagouti (a) to black-and-tan (a(t)) and white-bellied agouti (Aw) reveals alternative forms of agouti transcripts.

Bultman¹,

Klebig²,

Michaud³

et al. 1994

Genes Dev.

109

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“…1 Comparison with four other VL30 LTRs sequenced showed that the NVL-3 LTR had no discernible homology with the VL8 VL30 LTR, described by Itin and Keshet (22), which has weak promoter activity (41). There was, however, a closer relationship with the LTRs of clones VL3 (22), VL11 (22), and BVL-1 (19). The former of these is a strong promoter and was virtually identical to NVL-3 over the U3 (promoter) region but then diverged considerably throughout the 3' half of R and the US domain (Fig.…”

Section: Resultsmentioning

confidence: 82%

“…A typical element is 5.0 to 6.0 kilobases (kb) in length (8,19) with long terminal repeats (LTRs) of about 570 nucleotides ( Fig. 1) that resemble the LTRs of retroviruses (4,22,33).…”

mentioning

confidence: 99%

“…Recently, a number of VL30 LTRs were sequenced and shown to possess a typical retrovirus U3-R-U5 structure. Upstream of the RNA start site is a potential enhancer region that has homology with the murine sarcoma virus (MSV) enhancer (19) or the simian virus 40 (SV40) enhancer (33). Different LTRs have been shown to be transcriptionally active, although the efficiency varies between elements (41), possibly -reflecting differences in LTR structure.…”

mentioning

confidence: 99%

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Complete nucleotide sequence of a mouse VL30 retro-element.

Adams¹,

Rathjen²,

Stanway³

et al. 1988

Mol. Cell. Biol.

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The complete nucleotide sequence of a mouse retro-element is presented. The cloned element is composed of 4,834 base pairs (bp) with long terminal repeats of 568 bp separated by an internal region of 3,698 bp. The element did not appear to have any open reading frames that would be capable of encoding the functional proteins that are normally produced by retro-elements. However, some regions of the genome showed some homology to retroviral gag and pol open reading frames. There was no region in VL30 corresponding to a retroviral env gene. This implies that VL30 is related to retrotransposons rather than to retroviruses. The sequence also contained regions that were homologous to known reverse transcriptase priming sites and viral packaging sites. These observations, combined with the known transcriptional capacity of the VL30 promoter, suggest that VL30 relies on protein functions of other retro-elements, such as murine leukemia virus, while maintaining highly conserved cis-active promoter, packaging, and priming sites necessary for its replication and cell-to-cell transmission.The mouse VL30 elements are a family of dispersed retroviruslike DNA sequences that are present at about 200 copies per genome (24,25). A typical element is 5.0 to 6.0 kilobases (kb) in length (8, 19) with long terminal repeats (LTRs) of about 570 nucleotides (Fig. 1) that resemble the LTRs of retroviruses (4,22,33). VL30 elements fall into a broader class of murine sequences that constitutes a significant proportion of the mouse genome and includes the genomes of intracisternal A-type particles (1APs) (1,000 copies per genome) (29, 34) and the "early" transposons (300 to 500 copies per genome) (23). Structurally, these resemble eucaryotic retroviral proviruses and the retrotransposons of other eucaryotes, such as the Ty elements of yeasts (1, 16) and the copia-like elements of Drosophila spp. (31). Recent sequence information (29, 34) has shown that IAPs are most properly regarded as defective retroviruses. The status of VL30 elements is currently unknown.The major VL30 transcript is a characteristic 30S RNA which is expressed at relatively high levels and in a variety of cell types (2,7,21,26). This RNA varies between different elements but starts in the 5' LTR and terminates in the 3' LTR, so that it has a retroviruslike terminal redundancy (33). Recently, a number of VL30 LTRs were sequenced and shown to possess a typical retrovirus U3-R-U5 structure. Upstream of the RNA start site is a potential enhancer region that has homology with the murine sarcoma virus (MSV) enhancer (19) or the simian virus 40 (SV40) enhancer (33). Different LTRs have been shown to be transcriptionally active, although the efficiency varies between elements (41), possibly -reflecting differences in LTR structure. No VL30

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“…Furthermore, some vertebrate genetic elements, e.g. intracisternal A particle (IAP) genes (Ono et al, 1985), VL30 genes (Hodgson et al, 1983) and L1Md (Loeb et al, 1986), and transposable elements from other taxonomic groups [yeast Ty elements (Clare & Farabaugh, 1985;Hauber et al, 1985), Drosophila copia (Mount & Rubin, 1985) and copia-like elements (Saigo et al, 1984), Dictyostelium DIRS-1 element (Cappello et al, 1985), maize Bsl element (Johns et al, 1985), and possibly maize Cinl element (Shepherd et al, 1984)] have been shown to possess structural similarities to integrated retroviruses. The yeast Ty element transcript has recently been found to be contained within virus-like particles which have reverse transcriptase activity Mellor et al, 1985a).…”

Section: Introductionmentioning

confidence: 99%