Skip Navigation

This Article
Right arrow Abstract Freely available
Right arrow Print PDF (116K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (13)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Dej, K. J.
Right arrow Articles by Boeke, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dej, K. J.
Right arrow Articles by Boeke, J. D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research Pages 4019-4024  

A hotspot for the Drosophila gypsy retroelement in the ovo locus
Introduction
Materials And Methods
   Isolation of ovoD1 revertants
   PCR amplification
   DNA sequencing
Results And Discussion
   Introduction of gypsy to ovoD1 strains and identification of insertions
   Sequencing the insertion points of 26 gypsy elements in the ovo locus
   gypsy integration specificity
Acknowledgements
References

A hotspot for the Drosophila gypsy retroelement in the ovo locus

A hotspot for the Drosophila gypsy retroelement in the ovo locus

Kimberley J. Dej, Tatiana Gerasimova, Victor G. Corces and Jef D. Boeke1,*

Department of Biology, Johns Hopkins University and 1Department of Molecular Biology and Genetics,Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

Received April 24, 1998; Revised and Accepted July 22, 1998

ABSTRACT

The Drosophila retroelement gypsy has a number of unusual features including an unusual LTR terminal sequence and an apparent target sequence preference. The ovo locus is a known hotspot for gypsy insertion. We examined the target sequence preference of gypsy within ovo by isolating 26 new insertions and sequencing the gypsy/ovo junctions. Insertions were found at multiple sites within the ovo locus. The insertions clustered within an ~150 bp region in the non-translated region of the ovo[beta] transcript, with most insertions falling within the first intron. There were seven sites of insertion within this region and these mostly conform to the consensus sequence YRYRYR (where Y = pyrimidine and R = purine). However, this target sequence is at best necessary but not sufficient to specify a hotspot, as there were several other sequences conforming to this consensus in the ovo locus that were not hit. The results indicate that gypsy may have a higher degree of target specificity than most infectious LTR retroelements.

INTRODUCTION

The gypsy LTR retroelement of Drosophila melanogaster is of great interest because it represents a genetically tractable retroelement that is closely related to the non-infectious LTR retrotransposons but is infectious like retroviruses (1,2). Like retroviruses, gypsy encodes genes equivalent to gag, pol and env, whereas most retrotransposons encode only gag and pol. Moreover, the envelope protein is encoded by a subgenomic mRNA, just as is the case in retroviruses (3). The latter feature is shared with another Drosophila retroelement, Tom (4). Although this aspect of gypsy's biology has attracted considerable attention, relatively little is known about how gypsy, like all retrotransposons and retroviruses, inserts its DNA into the host genome during the essential integration phase of its life cycle. Like these other elements, gypsy encodes an integrase (IN) protein that presumably mediates the integration reaction. Unlike the other elements, gypsy has unusual terminal sequences, and may have sequence specificity for insertion.

LTR retroelement life cycles can be divided into a few discrete stages, reviewed in (5). These are: (i) the gene expression stage, when element RNA(s) and proteins are produced, (ii) the assembly stage, when virion or virus-like particles are put together and matured via a series of endoproteolytic cleavages, (iii) the reverse transcription stage, when element DNA is produced from the genomic RNA in the particle and (iv) the integration stage, during which the newly synthesized element DNA is integrated at a novel site in the host chromosome. An absolutely critical aspect of the integration stage is the identification of target sequences in host DNA. Craigie (6) pointed out that non-infectious elements are bound to the genome of the host organism they inhabit, and the progeny thereof. Hence non-infectious elements are likely to have evolved mechanisms for identifying `safe havens' in the host DNA where they do little if any damage to the host. In contrast, the infectious retroviruses are relatively free of this constraint because of their ability to move horizontally to other members of the host population. Indeed, recent studies of both avian and mammalian retroviral integration suggest that only modest specificity of integration relative to host DNA targets is observed (7,8). In contrast, recent studies of the integration specificity of the non-infectious elements Ty1, Ty3 and Ty5 of yeast have borne this prediction out rather spectacularly. Ty1 and Ty3 both target tRNA upstream regions, which in their host, Saccharomyces cerevisiae, represent gene-free `safe havens' (9-12). Interestingly Ty1 and Ty3, which are extremely distantly related elements (13), target these regions by what appear to be distinct mechanisms (14), and so tRNA targeting appears to be an example of convergent evolution for these two elements. Ty5 on the other hand, targets regions of silent chromatin, a different type of `safe haven' (15,16). Because the gypsy element lies at the phylogenetic interface between the retrotransposons and retroviruses, analysis of its integration specificity is of special interest.


Figure 1. Retroelement (LTR) termini. gypsy and related insect elements with three open reading frames corresponding to gag, pol and env have unusual termini relative to other retrotransposons and retroviruses, which universally begin and end with the dinucleotide inverted repeat TG ... CA. Interestingly, gypsy sequences from different Drosophila species do not completely conserve the terminal dinucleotide, suggesting that gypsy's IN may have less stringent terminal sequence requirements than those of the other LTR retroelements. Alternatively, the INs of different gypsy species could recognize the individual termini with high specificity.

The gypsy element is unusual among the LTR retroelements in another way. All retroviruses and nearly all LTR retrotransposons share the terminal sequences TG...CA (usually embedded within a somewhat longer imperfect, inverted repeat sequence; Fig. 1). However gypsy is one of a very small number of elements, thus far known only from insects, that have non-TG...CA terminal sequences. Interestingly, and perhaps not coincidentally, all of these elements share the property of having three reading frames corresponding to retroviral gag, pol and env. All of these elements are presumed to be infectious, although this has only been demonstrated, thus far, for gypsy.

The gypsy element can insert into many different loci in genomic DNA. Based on the sequencing of a relatively small number of genomic gypsy elements it was concluded that gypsy was highly sequence-specific in its insertion into genomic DNA; in nearly every example, the target sequence TATATA or TACATA (17-19) was duplicated upon insertion. A recent study in which three gypsy insertions into the ovo gene were sequenced (2) suggested that other target sequences could also be recognized, and suggested a relaxation of the proposed recognition sequence to YRYRYR. The gypsy element moves at high frequency during crosses of flamenco strains to other strains (20). A particularly useful genetic assay for gypsy movement was developed by Mével-Ninio et al. (21), who found that dominant alleles of the X-linked ovo locus, such as ovoD1, could be reverted by retrotransposon insertion. Our previous studies indicate that the ovo region represents a major hotspot for gypsy insertion, with as many as 1/4 of all insertions in the Drosophila genome occurring within this region (2). The ovo locus, required for differentiation of the female germ line, codes for two OVO protein isoforms that differ in their N-termini (22,23). Dominant female-sterile alleles, including ovoD1, are the result of point mutations that create new initiation codons in the 5[prime] region of ovo (24,25). We have used the ovoD1 reversion assay system to generate a larger collection of gypsy insertions, and report here the insertion sites of a total of 26 new insertion mutations within the ovo locus. Remarkably, almost all of the insertions recovered cluster within a region of ~150 bp and most of these fall within the first intron of the major ovo transcripts.

MATERIALS AND METHODS

Isolation of ovoD1 revertants

OvoD1 revertants were isolated by two methods, described in Figure 2. The two methods are genetic crosses (Fig. 2A) and virus particle `feeding' (Fig. 2B). In both the feeding experiments and the genetic crosses, the assay of ovoD1 reversion, originally described by Mével-Ninio et al. (21) and subsequently improved by identification of the flamenco gene as an essential element responsible for high level gypsy mobility (3,20), was used. The genetic crosses involved three steps. First, females of one of three strains, listed in Table 1, were crossed by y v f mal flam1 males (F0). Second, progeny females were crossed to ovoD1 v males (F1); the F2 female progeny were then scored for fertility (ovoD1 reversion). The high frequency of reversion observed (Table 1) indicates that the three strains from which the females were derived must bear flamenco mutations. In the feeding experiments, gypsy particles were first isolated from females of the y v f mal flam strain; these were fed to SS strain larvae as described previously (2).


Figure 2. Isolation of ovoD1 revertants caused by gypsy insertions (diagram of two methods, crossing and feeding). (A) Method 1: genetic cross. A genetic cross between females of a donor strain (y wa4 ct6 snw flam2) and ovoD1 males was carried out as outlined in the figure. Stocks of ovoDR (revertant) lines were then generated. (B) Method 2: `feeding' experiment. gypsy particles, isolated as described, were fed to the SS strain of flies. Fed SS females were mated with male ovoD1 flies and fertile female progeny were identified and studied further. PCR was performed on the DNA from the progeny of these ovoD1 (revertant) fertile females.

PCR amplification

Genomic DNA was prepared from 50 flies for each insertion stock by using a potassium acetate quickprep. Flies were homogenized in 500 µl of extraction buffer (0.1 M Tris-HCl, pH 9.0; 0.1 M EDTA; 1% SDS) using a glass mortar and pestle and the homogenate was incubated in a 1.5 ml microcentrifuge tube for 30 min at 70°C. Potassium acetate was added to a final concentration of ~0.1 M and the mixture was placed on ice for 30 min. This was spun down at 14 000 r.p.m. in an Eppendorf 5415C microfuge for 15 min at 4°C. The supernatant was transferred to a fresh 1.5 ml tube and the DNA was precipitated by adding 0.5× vol of isopropanol.

Approximately 50 ng of genomic DNA was used per PCR reaction. The PCR protocol was as follows: 91°C, 1 min; 58-62°C, 1 min; 72°C, 2-10 min; number of cycles, 32. Generally each sample was run for a short extension time (2-3 min) at 72°C with Taq polymerase and a long extension time (5-10 min) with Taq polymerase with Taq extender in order to look for short and long extension products. Taq polymerase and Taq polymerase extender buffers were used accordingly with 200 µM dNTPs and 10 ng/µl of each primer.

Primers used:

P1 5[prime]-CAACATGACCGAGGACGGTCATAAAC-3[prime] (gypsy 3[prime])
P2 5[prime]-CTCCCGCTCTGCGGGCTTCTCTTT-3[prime] (ovo 5[prime])
P3 5[prime]-CTTTGCCGAAAATATGCAATG-3[prime] (gypsy 5[prime])
P4 5[prime]-CGGCTTTTTCAGCGGCTAACC-3' (ovo 5[prime])
POA 5[prime]-TCGCCATCTCGCTCTGTTG-3[prime] (ovo 5[prime])
POB 5[prime]-CTCATTGCTCTACGCGTTCTG-3[prime] (ovo 3[prime])
POC 5[prime]-GCTACCAACCGAACAAGCTGC-3[prime] (ovo 3[prime])
SPGL5[prime]: 5[prime]-GCGTGGAGCGTTGAACCC-3[prime]
SPGL3[prime]: 5[prime]-TCAAGCCCTCCAACCTAA-5[prime]

Table 1. Frequency of ovoD1 reversion
Crosses
F0 female strain Total females tested Fertile F2 females ovoD1 reversion (%>
ctMR2 420 27 6.4
y wa4 ct6 snw 450 30 6.7
Df(1) Pgd-kz 397 12 3.1
Feeding
NA 928 20 2.2

PCR products were run on 0.8% agarose gels and these gels were dried and hybridized directly with ovo genomic DNA. The 18 kb ovo clone D1B2NR was used as a probe (26). This clone covers the 7.2 kb SalI-HindIII rescue fragment and 8 kb of upstream and 3 kb of downstream flanking DNA. PCR products that hybridized with the ovo DNA were then isolated from the gel by electroelution and sequenced directly.

The P4 and P2 primers and P4 and POB primers generated products of the expected length using genomic miniprep DNA as template (~1 and 6 kb respectively) showing that this protocol was capable of amplifying large products and thus of detecting any gypsy insertion within this region. Reactions were done using the Taq Extender PCR additive (Stratagene) which was used to generate up to an 8 kb product in control experiments using cloned DNA and vector primers.

DNA sequencing

PCR products were electroeluted from agarose gels and sequenced on an ABI Model 373 DNA sequencer using fluorescent dye terminator chemistry using the primers SPGL 5[prime] (reading outward from the 5[prime] LTR of gypsy) or SPGL 3[prime] (reading outward from the 3[prime] LTR of gypsy) as appropriate. When necessary, PCR products were directly cloned in the TA vector cloning system (InVitrogen, San Diego, CA) and the double-stranded plasmids were sequenced using the same method.

Figure 3. gypsy insertions in the ovo locus. The DNA sequence indicates the sites of insertion of gypsy in the ovo locus studied, as well as the features of the major ovo transcript found in the female germline, called variously the ovo[beta] and ovoB transcripts by different authors. This is the transcript relevant for the ovoD1 phenotype because ovoD1 only affects female fertility; a second transcript, ovo[alpha] or ovoA, is expressed in both sexes and has a different 5[prime] exon. The features included are the major transcription start site (TSS; vertical arrow), major and minor splice donor sites (SD; overline) for the first intron (two other extremely minor splice donors are not shown), the splice acceptor site in intron 1 (SA; overline), the position of the new ATG formed by the ovoD1 mutation (24,25) (arrow pointing upward) and a single gypsy insertion (site A, underline). Also indicated are seven sites of gypsy insertion uncovered during this study (sites B-H); the inferred target site duplications are underlined. The diagram indicates the position of sites A-H within the ovo locus; insertions are symbolized by triangles, exons by boxes and the ORF by shading. Rightward triangles are gypsy elements in the (+) orientation, leftward in the (-) orientation; the orientation of the insertion in site A has not been reported and is represented by a vertical triangle. The arrows below the number line indicate the approximate positions of the primers used.

RESULTS AND DISCUSSION

Introduction of gypsy to ovoD1 strains and identification of insertions

Insertions of gypsy into ovoD1 were obtained in either of two ways, by crossing as described (21) or by feeding of gypsy virus particles as described by Song et al. (2). The two methods used in this study are specifically outlined in Figure 2; in all cases a high level of ovoD1 reversion activity was observed (Table 1), and gypsy insertions constituted 61% of the total ovoD1 reversion events observed using both methods. The remaining (non-gypsy) revertants were not characterized further. The progeny of revertant female flies were studied for whether or not they bore gypsy elements within the ovo locus by a series of PCR amplification experiments using one primer reading outward from one of the gypsy ends and one primer chosen from among a set of primers spanning the ovo locus (Fig. 3). Finally, selected PCR products were chosen for DNA sequence analysis, and the DNA sequencing provided final proof that the observed products indeed corresponded to gypsy insertions into the ovo locus.

Sequencing the insertion points of 26 gypsy elements in the ovo locus

A total of 26 PCR products corresponding to gypsy-ovo junction fragments were directly sequenced (or cloned and then sequenced) and the sequences of the junction between the end of the gypsy element and ovo were tabulated (Fig. 3 and Table 2). Remarkably, all of the new insertion sites clustered within a 150 bp region, and seven different target sites, defined by their inferred 6 bp target site duplication, were observed; four of these target sites consisted of either a single insertion or insertions in a single orientation and the other three included insertions in both orientations. The (+) orientation (defined as the one in which gypsy and ovo are transcribed in the same direction) was represented by 62% of the insertions. All but one of the newly defined target sites fall within the first intron of the female germ line-specific ovo[beta] transcripts of the ovo locus recently defined by Garfinkel et al. (23) and Mével-Ninio et al. (24). The remaining target site lies at the major ovo[beta] transcription start site mapped in the same studies. All of the insertions lie within the boundaries of the other class of transcripts, the ovo[alpha] transcript. Interestingly, the yct allele contains two separate gypsy insertions ~40 bp apart, in opposite orientations. The insertion sites obtained by crossing and feeding methods were very similar to each other, and also agree well with the positions of previously restriction mapped insertions (1,21).

Table 2. Consensus sequence of target site duplication
Consensus % of insertions conforming
TATATA 0
TACATA 6.7
YRYRYR 67
YRYRYR 5/6 match 23

It is expected that insertion of gypsy at these positions in ovo will lead to premature termination of transcription within the gypsy sequences. The ovo locus contains two transcription start sites at positions 361 and 852 bp (22). The transcript initiating at 361 bp codes for the OVO-A isoform, a 1222 amino acid protein believed to be expressed late in oogenesis (25). The second transcript codes for the OVO-B isoform, a smaller protein truncated at its N-terminus. The OVO-B isoform is believed to be expressed early in oogenesis (25). It has been suggested that the expression of OVO-A may downregulate OVO-B late in oogenesis. Several dominant female sterile alleles of ovo, such as ovoD1, result from point mutations that create new in-frame translation initiator codons upstream of the OVO-B initiator site and result in translation of a new protein with an N-terminal extension (24,25). This new protein is thought to act like OVO-A and downregulate OVO-B; however, the mutant OVO-D isoform would be expressed inappropriately early in oogenesis and downregulation of OVO-B would occur prematurely, resulting in female sterility. Insertion of gypsy sequences that terminates transcription of the ovoD1 mRNA would prevent production of the OVO-D isoform and restore fertility.

Table 3. gypsy insertion alleles recovered at ovo
Allele name Sitea Target site duplicationb Orientation in ovoc Isolation methodd PCR primerse
lzl A TACATA NR NR (23)
75-1 C TGTGCA + 2 p3, p4
ct5 B GTAAAA + 1 p3, p4
ct17 B GTAAAA + 1 p3, p4
ct16 C TGCACA - 1 p1, p4
ct28 C TGTGCA + 1 p3, p4
ct31 C TGCACA - 1 p1, p4
ct61 C TGCACA - 1 p1,p4
ct67 C TGCACA - 1 p1, p4
Df4 C TGCACA - 1 p1, p4
f2 C TGTGCA + 2 p3, p4
f5-1 C TGCACA - 2 p1, p4
f28-3 C TGCACA - 2 p1, p4
X C TGTGCA + 2 p3, p4
Y C TGTGCA + 2 p3, p4
R11 D TGCACTf - 2 (2) p1, p2
yct D TGCACTf - 1 p3, pC
ct37 E TGGAAC + 1 p3, p4
5-1 F TATAAAf + 2 p3, p4
ct8 F TATAAAf + 1 p3, p4
f30-3 F TATAAAf - 2 p1, p4
yct F TATAAAf + 1 p1, p4
Z F TATAAAf + 2 p3, p4
ct7 G TATACA + 1 p3, p4
ct19 G TATACA + 1 p3, p4
ct30 G TATACA + 1 p3, p4
ct45 G TATACA + 1 p3, p4
ct90 G TGTATA - 1 p1, p4
R15 G TATACA + 2 (2) p3, p2
R9 H TACATA + 2 (2) p1, p2
aSee Figure 3; the yct allele apparently contains two separate gypsy insertions in opposite orientations.
bInferred from sequence of a single junction.
c+, gypsy and ovo transcribed in same direction; -, gypsy and ovo transcribed in opposite directions; NR, not reported.
d1, genetic cross; 2, `feeding' experiment (Fig. 2).
eSee figures 3 or 6 in Song et al. (2) as indicated.
fSingle mismatch with YRYRYR consensus (Table 3).

We hypothesize that insertion of gypsy at these positions will lead to the premature termination of ovo transcription within the gypsy sequences. This is expected to be the case in the (+) orientation, in which the LTR termination sequences will be in their active orientation. It is not known whether gypsy inserted in the opposite orientation will result in truncation of the ovo mRNA, but we note that there are four copies of the sequence AATAAA, a sequence known to specify polyadenylation, on the negative strand of the gypsy sequence. We believe these gypsy insertions may represent null alleles (or at least alleles that significantly reduce ovoD1 expression) because they phenotypically completely reverse the dominant female-sterile phenotype of the starting ovoD1 mutation.

gypsy integration specificity

Examination of the target sites within the ovo gene reveals that the previously reported `consensus sequences' for gypsy, namely TATATA and TACATA, are poorly represented among the collection of ovo insertions sequenced (Table 3). However, if the consensus is relaxed to a slightly more degenerate one consisting of alternating pyrimidine (Y) and purine (R) residues, that is, a YRYRYR consensus target sequence, it is apparent that most of the ovo insertions conform. If this requirement is further relaxed by allowing a single mismatch to the consensus, ~90% of the insertions conform (as do all previously reported gypsy target site sequences). Interestingly, all of the single mismatches in our studies were in the 5th or 6th position of the target site duplication. The alternating purines and pyrimidines are a typical feature of DNA sequences able to adopt the Z conformation (27), raising the possibility that gypsy recognizes this DNA structural feature. Alternatively, othersequence variations, such as kinks have been associated with YR steps in DNA sequences (28), and these could conceivably be recognized by the gypsy integration machinery. Site C, our biggest hotspot, lies within a stretch of 11 alternating pyrimidines and purines and sites F, G and H lie within stretches of 10.

However, the target sequence and/or Z-DNA are unlikely to fully explain gypsy integration specificity in the ovo locus because there are many other sequences within ovo that conform to the consensus and yet do not appear in our collection of insertion mutations. In particular, there is a remarkable sequence of 39 consecutive alternating pyrimidines and purines (nt 184-222) that was not hit in our study, although a single insertion in this region has been reported previously as a mutation that reverts ovoD1 (23,29). Furthermore, our earlier study suggests that as many as 1/4 of all gypsy insertions occur within the ovo region cytologically (2). Thus, the gypsy integration machinery must recognize features of this region other than simply the DNA sequence or Z-DNA structure. In any case, it is very clear that gypsy sequences integrate very non-randomly in response to the selection for ovoD1 revertants.

ACKNOWLEDGEMENTS

We thank Maryellen Kurkulos for helpful discussions and Sun Song for doing some of the feeding experiments. Supported in part by NIH grant CA16519 (J.D.B.) and GM56022 (V.G.C.).

REFERENCES

1. Kim,A.I., Terzian,C., Santamaria,P., Pélisson,A., Prud'homme,N. and Bucheton,A. (1994) Proc. Natl Acad. Sci. USA, 91, 1285-1289.

2. Song,S.U., Gerasimova,T., Kurkulos,M., Boeke,J.D. and Corces,V.G. (1994) Genes Dev., 8, 2046-2057. MEDLINE Abstract

3. Pélisson,A., Song,S.U., Prud'homme,N., Smith,P., Bucheton,A. and Corces,V.G. (1994) EMBO J., 8, 4401-4411.

4. Tanda,S., Mullor,J.L. and Corces,V.G. (1994) Mol. Cell. Biol., 14, 5392-5401. MEDLINE Abstract

5. Boeke,J.D. and Stoye,J.P. (1997) In Varmus,H., Hughes,S. and Coffin,J. (eds), Retroviruses. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 343-435.

6. Craigie,R. (1992) Trends Genet., 8, 187-189. MEDLINE Abstract

7. Carteau,S.C.H. and Bushman,F. (1998) J. Virol., 72, 4005-4014. MEDLINE Abstract

8. Withers-Ward,E.S., Kitamura,Y., Barnes,J.P. and Coffin,J.M. (1994)Genes Dev., 8, 1473-1487. MEDLINE Abstract

9. Chalker,D.L. and Sandmeyer,S.B. (1990) Genetics, 126, 837-850. MEDLINE Abstract

10. Chalker,D.L. and Sandmeyer,S.B. (1992) Genes Dev., 6, 117-128. MEDLINE Abstract

11. Devine,S.E. and Boeke,J.D. (1994) Nucleic Acids Res., 18, 3765-3772.

12. Ji,H., Moore,D.P., Blomberg,M.A., Braiterman,L.B., Voytas,D.F., Natsoulis,G. and Boeke,J.D. (1993) Cell, 73, 1007-1018. MEDLINE Abstract

13. Xiong,Y. and Eickbush,T.H. (1990) EMBO J., 9, 3353-3362. MEDLINE Abstract

14. Boeke,J.D. and Devine,S.E. (1998) Cell, 93, 1087-1089. MEDLINE Abstract

15. Gai,X. and Voytas,D.F. (1998) Mol. Cell, 1, 1051-1055.

16. Zou,S., Ke,N., Kim,J.M. and Voytas,D.F. (1996) Genes Dev., 10, 634-645. MEDLINE Abstract

17. Freund,R. and Meselson,M. (1984) Proc. Natl Acad. Sci. USA, 81, 4462-4464. MEDLINE Abstract

18. Bayev,A.A.,Jr, Lyubomirskaya,N.V., Dzhumagaliev,E.B., Ananiev,E.V., Amiantova,I.G. and Ilyin,Y.V. (1984) Nucleic Acids Res., 12, 3707-3723. MEDLINE Abstract

19. Marlor,R.L., Parkhurst,S.M. and Corces,V.G. (1986) Mol. Cell. Biol., 6, 1129-1134. MEDLINE Abstract

20. Prud'homme,N., Gans,M., Masson,M., Terzian,C. and Bucheton,A. (1995) Genetics, 139, 697-711. MEDLINE Abstract

21. Mével-Ninio,M., Mariol,C.M. and Gans,M. (1989) EMBO J., 8, 1549-1558.

22. Mével-Ninio,M., Terracol,R., Salles,C., Vincent,A. and Payre,F. (1995) Mech. Dev., 49, 83-95. MEDLINE Abstract

23. Garfinkel,M.D., Wang,J., Liang,Y. and Mahowald,A.P. (1994)Mol. Cell. Biol., 14, 6809-6818. MEDLINE Abstract

24. Mével-Ninio,M., Fouilloux,E., Guénal,I. and Vincent,A. (1996) Development, 122, 4131-4138. MEDLINE Abstract

25. Andrews,J., Levenson,J. and Oliver,B. (1997) Dev. Genes. Evol., 207, 482-487.

26. Chou,T.B., Noll,E. and Perrimon,N. (1993) Development, 119, 1359-1369. MEDLINE Abstract

27. Haniford,D.B. and Pulleyblank,D.E. (1983) J. Biomol. Struct. Dynam., 1, 593-609.

28. Dickerson,R.E. (1998) Nucleic Acids Res., 26, 1906-1926. MEDLINE Abstract

29. Garfinkel,M.D., Lohe,A.R. and Mahowald,A.P. (1992) Genetics, 130, 791-803. MEDLINE Abstract

*To whom correspondence should be addressed at: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine,617 Hunterian, 725 N. Wolfe Street, Baltimore, MD 21205, USA. Tel: +1 410 955 2481; Fax: +1 410 614 2987; Email: jef.boeke@qmail.bs.jhu.edu

This page is run by Oxford University Press, Great Clarendon Street, Oxford OX2 6DP, as part of the OUP Journals
Comments and feedback: www-admin{at}oup.co.uk
Last modification: 14 Aug 1998
Copyright©Oxford University Press, 1998.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 GeneticsHome page
M. Labrador, K. Sha, A. Li, and V. G. Corces
Insulator and Ovo Proteins Determine the Frequency and Specificity of Insertion of the gypsy Retrotransposon in Drosophila melanogaster
Genetics, November 1, 2008; 180(3): 1367 - 1378.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
E. Glasscock and M. A. Tanouye
Drosophila couch potato Mutants Exhibit Complex Neurological Abnormalities Including Epilepsy Phenotypes
Genetics, April 1, 2005; 169(4): 2137 - 2149.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
C. S. Copeland, P. J. Brindley, O. Heyers, S. F. Michael, D. A. Johnston, D. L. Williams, A. C. Ivens, and B. H. Kalinna
Boudicca, a Retrovirus-Like Long Terminal Repeat Retrotransposon from the Genome of the Human Blood Fluke Schistosoma mansoni
J. Virol., June 1, 2003; 77(11): 6153 - 6166.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
M. Labrador and V. G. Corces
Protein Determinants of Insertional Specificity for the Drosophila Gypsy Retrovirus
Genetics, July 1, 2001; 158(3): 1101 - 1110.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
J Lu and B Oliver
Drosophila OVO regulates ovarian tumor transcription by binding unusually near the transcription start site
Development, January 5, 2001; 128(9): 1671 - 1686.
[Abstract] [PDF]

Home page
 Genome ResHome page
N. J. Bowen and J. F. McDonald
Genomic Analysis of Caenorhabditis elegans Reveals Ancient Families of Retroviral-like Elements
Genome Res., October 1, 1999; 9(10): 924 - 935.
[Abstract] [Full Text]

Home page
 J. Virol.Home page
P. Leblanc, B. Dastugue, and C. Vaury
The Integration Machinery of ZAM, a Retroelement from Drosophila melanogaster, Acts as a Sequence-Specific Endonuclease
J. Virol., August 1, 1999; 73(8): 7061 - 7064.
[Abstract] [Full Text]

Home page
 J. Virol.Home page
H. S. Malik and T. H. Eickbush
Modular Evolution of the Integrase Domain in the Ty3/Gypsy Class of LTR Retrotransposons
J. Virol., June 1, 1999; 73(6): 5186 - 5190.
[Abstract] [Full Text]

This Article
Right arrow Abstract Freely available
Right arrow Print PDF (116K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (13)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Dej, K. J.
Right arrow Articles by Boeke, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dej, K. J.
Right arrow Articles by Boeke, J. D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?