Primary structure and expression of the xiphophorus DNA-(cytosine-5)-methyltransferase XDNMT-1.
Small aquarium fishes become increasingly important in the study of normal vertebrate development and disease. Differential DNA methylation might play a role in these processes. In the teleost Xiphophorus, a well-established animal model for melanoma formation, tumour-specific hypomethylation of the melanoma-inducing gene ONC-Xmrk has been observed. We have isolated a cDNA for the DNA-(cytosine-5)-methyltransferase XDNMT-1 from this organism, which encodes the first full-length protein from a fish species. Linkage analysis showed that Xdnmt-1 is different from the Xiphophorus tumour suppressor R, which is involved in the transcriptional repression of the ONC-Xmrk melanoma oncogene in healthy fish. As methylation has been implicated in the regulation of ONC-Xmrk expression, XDNMT-1 might play a role by acting up- or downstream of R. Expression analysis demonstrated that the Xdnmt-1 transcript is present in all adult tissues and cell lines tested. However, developing embryos show a spatially and temporally regulated expression pattern suggesting that the enzyme might play a role during development in fish.
Altschmied
J
J
Department of Physiological Chemistry I, Biocenter (Theodor Boveri Institute), University of Würzburg, Am Hubland, Germany. altschmied@em.uni-frankfurt.de
Volff
J N
JN
Winkler
C
C
Gutbrod
H
H
Körting
C
C
Pagany
M
M
Schartl
M
M
D000818:Animals; D002460:Cell Line; D003532:Cyprinodontiformes / Q000196:embryology / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D005260:Female; D029941:Fish Proteins; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D008040:Genetic Linkage; D017403:In Situ Hybridization; D008297:Male; D008545:Melanoma / Q000235:genetics; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D029941:Fish Proteins; D004247:DNA; D004248:DNA (Cytosine-5-)-Methyltransferases; D020794:Receptor Protein-Tyrosine Kinases; C077101:Xmrk protein, Xiphophorus