Comparative sequence analysis of the imprinted Dlk1-Gtl2 locus in three mammalian species reveals highly conserved genomic elements and refines comparison with the Igf2-H19 region.
[en] The Dlk1-Gtl2 domain on mouse chromosome 12 contains reciprocally imprinted genes with the potential to contribute to our understanding of common features involved in imprinting control. We have sequenced this conserved region in the mouse and sheep and included the human sequence in a three species comparison. This analysis resulted in a precise conservation map and identification of highly conserved sequence elements, some of which we have shown previously to be differentially methylated in the mouse. Additionally, this analysis facilitated identification of a CpG-rich tandem repeat array located approximately 13-15 kb upstream of Gtl2. Furthermore, we have identified a third imprinted transcript that overlaps with the last Dlk1 exon in the mouse. This transcript lacks a conserved open reading frame and is probably generated by cleavage of extended Dlk1 transcripts. Because Dlk1 and Gtl2 share many of the imprinting properties of the well-characterized Igf2-H19 domain, it has been proposed that the two regions may be regulated in the same way. Comparative genomic examination of the two domains indicates that although there are similarities, other features are very different, including the location of conserved CTCF-binding sites, and the level of conservation at regulatory regions.
Disciplines :
Genetics & genetic processes
Author, co-author :
Paulsen, M.
Takada, S.
Youngson, N. A.
Benchaib, M.
SEGERS, Karin ; Université de Liège - ULiège > CSL (Centre Spatial de Liège)
Ferguson-Smith, A. C.
Georges, Michel ; Université de Liège - ULiège > Département de productions animales > GIGA-R : Génomique animale
Charlier, Carole ; Université de Liège - ULiège > Département de productions animales > GIGA-R : Génomique animale
Language :
English
Title :
Comparative sequence analysis of the imprinted Dlk1-Gtl2 locus in three mammalian species reveals highly conserved genomic elements and refines comparison with the Igf2-H19 region.
Publication date :
2001
Journal title :
Genome Research
ISSN :
1088-9051
eISSN :
1549-5469
Publisher :
Cold Spring Harbor Laboratory Press, Cold Spring Harbor, United States - New York
Ainscough J.F.X., John R.M., Barton S.C., Surani M.A. (2000) A skeletal muscle-specific mouse Igf2 repressor lies 40 kb downstream of the gene. Development 127:3923-3930.
Bailey J.A., Carrel L., Chakravarti A., Eichler E.E. (2000) Molecular evidence for a relationship between LINE-1 elements and X chromosome inactivation: The Lyon repeat hypothesis. Proc. Natl. Acad. Sci. 97:6634-6639.
Bell A.C., Felsenfeld G. (2000) Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 405:482-485.
Berghmans S., Segers K., Shay T., Georges M., Cockett N.E., Charlier C. (2000) Breakpoint mapping positions of the callipyge gene within a 450 kilobase chromosome segment containing the Gtl2 gene. Mamm. Genome 12:183-185.
Boccaccio I., Glatt-Deeley H., Watrin F., Roeckel N., Lalande M., Muscatelli F. (1999) The human MAGEL2 gene and its mouse homologue are paternally expressed and mapped to the Prader-Willi region. Hum. Mol. Genet. 8:2497-2505.
Charlier C., Segers K., Karim L., Shay T., Gyapay G., Cockett N., Georges M. (2001) Human-ovine comparative sequencing of a 250 kilobase imprinted domain encompassing the clpg gene and identification of six imprinted transcripts: DLK1, GTL2, DAT, PERL, antiPERL, and MEGC. Genome Res. 11:850-862.
Chomczynski P., Sacchi N. (1987) Single step method of RNA isolation by acid Guanidinium Thiocyanate-Phenol-Chloroform extraction. Anal. Biochem. 162:156-159.
DeChiara T.M., Robertson E.J., Efstratiadis A. (1991) Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64:849-859.
Dubchak I., Brudno M., Loots G.G., Pachter L., Mayor C., Rubin E.M., Frazer K.A. (2000) Active conservation of noncoding sequences revealed by three-way species comparisons. Genome Res. 10:1304-1306.
Eggenschwiler J., Ludwig T., Fisher P., Leighton P.A., Tilghman S.M., Efstratiadis A. (1997) Mouse mutant embryos overexpressing IGF-II exhibit phenotypic features of the Beckwith-Wiedemann and Simpson-Golabi-Behmel syndromes. Genes & Dev. 11:3128-3142.
Engemann S., Strödicke M., Paulsen M., Franck O., Reinhardt R., Lane N., Reik W., Walter J. (2000) Sequence and functional comparison in the Beckwith-Wiedemann region: Implications for a novel imprinting centre and extended imprinting. Hum. Mol. Genet. 9:2691-2706.
Feil R., Walter J., Allen N.D., Reik W. (1994) Developmental control of allelic methylation in the imprinted mouse Igf2 and H19 genes. Development 120:2933-2943.
Ferguson-Smith A.C., Cattanach B.M., Barton S.C., Beechey C.V., Surani M.A. (1991) Embryological and molecular investigations of parental imprinting on mouse chromosome 7. Nature 351:667-670.
Ferguson-Smith A.C., Sasaki H., Cattanach B.M., Surani M.A. (1993) Parental-origin-specific epigenetic modification of the mouse H19 gene. Nature 22:751-755.
Gautier C. (2000) Compositional bias in DNA. Curr. Opin. Genet. Dev. 10:656-661.
Georgiades P., Chierakul C., Ferguson-Smith A.C. (1998) Parental origin effects in human trisomy for chromosome 14q: Implications for genomic imprinting. J. Med. Genet. 35:821-824.
Georgiades P., Watkins M., Surani M.A., Ferguson-Smith A.C. (2000) Parental origin-specific developmental defects in mice with uniparental disomy for chromosome 12. Development 127:4719-4728.
Georgiades P., Watkins M., Burton G., Ferguson-Smith A.C. (2001) Roles for genomic imprinting and the zygotic genome in placental development. Proc. Natl. Acad. Sci. 98:4522-4527.
Kanduri C., Pant V., Loukinov D., Pugacheva E., Qi C.F., Wolffe A., Ohlsson R., Lobanenkov V.V. (2000) Functional association of CTCF with the insulator upstream of the H19 gene is parent of origin-specific and methylation-sensitive. Curr. Biol. 13:853-856.
Leighton P.A., Saam J.R., Ingram R.S., Stewart C.L., Tilghman S.M. (1995) An enhancer deletion affects both H19 and Igf2 expression. Genes & Dev. 9:2079-2089.
Lyon M.F. (1998) X-chromosome inactivation: A repeat hypothesis. Cytogenet. Cell. Genet. 80:133-137.
Madsen O., Scally M., Douady C.J., Kao D.J., DeBry R.W., Adkins R., Amrine H.M., Stanhope M.J., De Jong W.W., Springer M.S. (2001) Parallel adaptive radiations in two major clades of placental mammals. Nature 409:610-614.
Miyoshi N., Wagatsuma H., Wakana S., Shiroishi T., Nomura M., Aisaka K., Kohda T., Surani M.A., Kaneko-Ishino T., Ishino F. (2000) Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q. Genes Cells 5:211-220.
Murphy W.J., Eizirik E., Johnson W.E., Zhang Y.P., Ryder O.A., O'Brien S.J. (2001) Molecular phylogenetics and the origins of placental mammals. Nature 409:614-618.
Okamura K., Hagiwara-Takeuchi Y., Li T., Vu T.H., Hirai M., Hattori M., Sakaki Y., Hoffman A.R., Ito T. (2000) Comparative genome analysis of the mouse imprinted gene Impact and its nonimprinted human homolog IMPACT: Toward the structural basis of species-specific imprinting. Genome Res. 10:1878-1889.
Onyango P., Miller W., Lehoczky J., Leung C.T., Birren B., Wheelan S., Dewar K., Feinberg A.P. (2000) Sequence and comparative analysis of the mouse 1-Megabase region orthologous to the human 11p15 imprinted domain. Genome Res. 10:1697-1710.
Paulsen M., El-Maari O., Engemann S., Strödicke M., Franck O., Davies K., Reinhardt R., Reik W., Walter J. (2000) Sequence conservation and variability of imprinting in the Beckwith-Wiedemann syndrome gene cluster in human and mouse. Hum. Mol. Genet. 9:1829-1841.
Sambrook J., Fritsch E., Maniatis T. Molecular Cloning: A Laboratory Manual, (second edition). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.; 1989.
Sasaki H., Jones P.A., Chaillet J.R., Ferguson-Smith A.C., Barton S.C., Reik W., Surani M.A. (1992) Parental imprinting: Potentially active chromatin of the repressed maternal allele of the mouse insulin-like growth factor II (Igf2) gene. Genes & Dev. 6:1843-1856.
Scheper W., Meinsma D., Holtzhuizen P.E., Sussenbach J.S. (1995) Long-range RNA interaction of two sequence elements required for endonucleolytic cleavage of human insulin-like growth factor II mRNAs. Mol. Cell. Biol. 15:235-245.
Schmidt J.V., Matteson P.G., Jones B.K., Guan X.J., Tilghman S.M. (2000) The Dlk1 and Gtl2 genes are linked and reciprocally imprinted. Genes & Dev. 14:1997-2002.
Schuster-Gossler K., Simon D., Guénet J.-L., Zachgo J., Gossler A. (1996) Gtl2lacZ an insertional mutation on mouse Chromosome 12 with parental origin-dependent phenotype. Mammalian Genome 7:20-24.
Schuster-Gossler K., Bilinksi P., Sado T., Ferguson-Smith A., Gossler A. (1998) The mouse Gtl2 gene is differentially expressed during embryonic development, encodes multiple alternatively spliced transcripts, and may act as an RNA. Dev. Dyn. 212:214-228.
Schwartz S., Zhang Z., Frazer K.A., Smit A., Riemer C., Bouck J., Gibbs R., Hardison R., Miller W. (2000) PipMaker-A web server for aligning two genomic DNA sequences. Genome Res. 10:577-586.
Smit A.F.A. (1999) Interspersed repeats and other mementos of transposable elements in mammalian genomes. Curr. Opin. Genet. Dev. 9:657-663.
Sun F.L., Dean W.L., Kelsey G., Allen N.D., Reik W. (1997) Transactivation of Igf2 in a mouse model of Beckwith-Wiedemann syndrome. Nature 389:809-815.
Sutton V.R., Shaffer L.G. (2000) Search for imprinted regions on chromosome 14: Comparison of maternal and paternal UPD cases with cases of chromosome 14 deletion. Am. J. Med. Genet. 93:381-387.
Szabo P., Tang S.H., Rentsendorj A., Pfeifer G.P., Mann J.R. (2000) Maternal-specific footprints at putative CTCF sites in the H19 imprinting control region give evidence for insulator function. Curr. Biol. 10:607-610.
Takada S., Tevendale M., Baker J., Georgiades P., Campbell E., Freeman T., Johnson M.H., Paulsen M., Ferguson-Smith A.C. (2000) Dlk (Delta-like) and Gtl2 are closely linked reciprocally imprinted genes on mouse chromosome 12 and are paternally methylated and co-expressed during development. Curr. Biol. 10:1135-1138.
Wylie A.A., Murphy S.K., Orton T.C., Jirtle R.L. (2000) Novel imprinted DLK1/GTL2 domain on human chromosome 14 contains motifs that mimic those implicated in Igf2/H19 regulation. Genome Res. 10:1711-1718.