Journal of Molecular Biology
Volume 203, Issue 4, 20 October 1988, Pages 971-983
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Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells: The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases

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Abstract

A cDNA encoding DNA (cytosine-5)-methyltransferase (DNA MeTase) of mouse cells has been cloned and sequenced. The nucleotide sequence contains an open reading frame sufficient to encode a polypeptide of 1573 amino acid residues, which is close to the apparent size of the largest species of DNA MeTase found in mouse cells. The carboxyl-terminal 570 amino acid residues of the inferred protein sequence shows striking similarities to bacterial type II DNA cytosine methyltransferases and appears to represent a catalytic methyltransferase domain. The amino-terminal portion of the molecule may be involved in regulating the activity of the carboxyl-terminal methyltransferase domain, since antibodies directed against a peptide sequence located within this region inhibits transmethylase activity in vitro. A 5200 base DNA MeTase-specific mRNA was found to be expressed in all mouse cell types tested, and cell lines known to have different genomic methylation patterns were found to contain DNA MeTase proteins of similar or identical sizes and de novo sequence specificities. The implications of these findings for an understanding of the mechanisms involved in the establishment and maintenance of methylation patterns are discussed.

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    This work was supported by grants from the National Institutes of Health.

    Present address: Department of Anatomy and Cellular Biology, Harvard Medical School, 45 Shattuck Street, Boston, MA 02115, U.S.A.

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