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Titolo:
Identification of a novel member of the Snail/Gfi-1 repressor family, mlt 1, which is methylated and silenced in liver tumors of SV40 T antigen transgenic mice
Autore:
Tateno, M; Fukunishi, Y; Komatsu, S; Okazaki, Y; Kawai, J; Shibata, K; Itoh, M; Muramatsu, M; Held, WA; Hayashizaki, Y;
Indirizzi:
RIKEN, Genom Sci Ctr, Genome Explorat Res Grp, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan RIKEN Yokohama Kanagawa Japan 2300045 , Yokohama, Kanagawa 2300045, Japan CREST, Japan Sci & Technol Corp, Tsukuba, Ibaraki 3050074, Japan CREST Tsukuba Ibaraki Japan 3050074 Corp, Tsukuba, Ibaraki 3050074, Japan RIKEN, Genome Sci Lab, Tsukuba, Ibaraki 3050074, Japan RIKEN Tsukuba Ibaraki Japan 3050074 Lab, Tsukuba, Ibaraki 3050074, Japan Univ Tsukuba, Cooperat Grad Sch Med, Tsukuba, Ibaraki 3050006, Japan Univ Tsukuba Tsukuba Ibaraki Japan 3050006 sukuba, Ibaraki 3050006, Japan Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Buffalo, NY 14263 USA Roswell Pk Canc Inst Buffalo NY USA 14263 lar Biol, Buffalo, NY 14263 USA
Titolo Testata:
CANCER RESEARCH
fascicolo: 3, volume: 61, anno: 2001,
pagine: 1144 - 1153
SICI:
0008-5472(20010201)61:3<1144:IOANMO>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
ZINC-FINGER PROTEIN; DNA METHYLATION; TRANSCRIPTIONAL REPRESSOR; GENOMIC DNA; GENE; MOUSE; EXPRESSION; CELLS; DIFFERENTIATION; METHYLTRANSFERASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Hayashizaki, Y RIKEN, Genom Sci Ctr, Genome Explorat Res Grp, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan RIKEN 1-7-22 Suehiro Cho Yokohama Kanagawa Japan 2300045 an
Citazione:
M. Tateno et al., "Identification of a novel member of the Snail/Gfi-1 repressor family, mlt 1, which is methylated and silenced in liver tumors of SV40 T antigen transgenic mice", CANCER RES, 61(3), 2001, pp. 1144-1153

Abstract

DNA methylation is the only known mechanism for an epigenetic genomic DNA modification that is capable of altering gene expression. A recent study reveals that the pattern of CpG island methylation is largely characteristic of tumor type, suggesting that distinct sets of genes are inactivated by methylation during development of each tumor type. We compared previously themethylation status between normal liver and liver tumors in SV40 T/t antigen transgenic mice (MT-D2 mice) using Restriction Landmark Genomic Scanningfor Methylation (RLGS-M) and identified several loci/spots that appeared to be methylated frequently in liver tumors. One of these spots, B236, identified a locus on chromosome 12 (D12Ncvs7) syntenic with human 14q12-q21 that is frequently Lost in certain human cancers. Shotgun sequencing of a bacterial artificial chromosome clone containing this spot/locus was performed to identify genes within this region. The Genescan program predicted an open reading frame of a novel, intron-less gene adjacent to the B236 spot thatencodes a putative 493-amino acid protein containing the SNAG repressor motif in the NH2-terminal region and five C2H2-type zinc finger motifs in theCOOH-terminal half. This putative gene, methylated in liver lumor (mlt 1),is a novel member of the SNAG transcriptional repressor family with 43% amino acid identity to insulinoma-associated protein 1. An open reading frameencoding a protein quite similar to mouse mlt 1 (56% amino acid identity) was located in the syntenic region of the human genome, indicating that mlt1 is evolutionarily conserved in human. Northern blot analysis revealed that mlt 1 is normally expressed in brain, spleen, stomach, and liver, However, mlt 1 expression was silenced in the liver tumors of MT-D2 mice. The putative promoter region of mlt 1 is unmethylated in normal tissues but methylated in all liver tumors from 11 MT-D2 mice. We also found that mlt 1 was methylated and not expressed in N18TG-2 cells, a mouse neuroblastoma cell line. Treatment of N18TG-2 tells with a demethylating agent, 5-aza-deoxycytidine, resulted in an expression of mlt 1, indicating that the repression of mlt 1 is attributable to methylation. Thus, mlt 1 is a novel target gene that is silenced by methylation during liver tumorigenesis initiated by SV40 T antigen.

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Documento generato il 19/09/20 alle ore 14:55:41