Abstract
Abstract Alignment of vertebrate and invertebrate DNA methyltransferases 2 (Dnmt2) evidenced an overall evolutionary conservation of these proteins. However, alignment revealed a vertebrate-specific stretch of about forty amino acids located between the catalytic motif VIII and the target recognition domain that is constantly absent from insect homologues. The analysis of the three-dimensional structure of DNA methyltransferase indicated that this vertebrate specific Dnmt2 portion is located at the DNA binding domain whose structure is essential for the discrimination of the proper target sequence. Insect Dnmt2 enzymes are, therefore, devoid of a portion of the DNA binding domain suggesting that this structural change may alter the methylation target of insect Dnmt2 making cytosine methylation not limited to the vertebrate canonical CpG but extended to cytosine residues belonging to other dinucleotides.
Highlights
It is well known that a variable portion of cytosine residues is methylated in the form of 5-methylcytosine in eukaryotic genomes (Bird 2002)
Loss of function mutations of DNA methyltransferases 2 (Dnmt2) gene did not showed any effect on mice genomic methylation patterns (Okano et al 1998) on the contrary of what happen with mutations in Dnmt1 that resulted in developmental defects (Li et al 1992; Lei et al 1996)
D.melanogaster, D. pseudoobscura and A.gambiae genome project revealed that Dnmt2 proteins represent the only candidates DNA methyltransferases suggesting that this enzyme could be the unique responsible for DNA methylation in insect genomes (Kunert et al 2003; Marhold et al 2004)
Summary
Abstract — Alignment of vertebrate and invertebrate DNA methyltransferases 2 (Dnmt2) evidenced an overall evolutionary conservation of these proteins. Alignment revealed a vertebrate-specific stretch of about forty amino acids located between the catalytic motif VIII and the target recognition domain that is constantly absent from insect homologues. The analysis of the three-dimensional structure of DNA methyltransferase indicated that this vertebrate specific Dnmt portion is located at the DNA binding domain whose structure is essential for the discrimination of the proper target sequence. Insect Dnmt enzymes are, devoid of a portion of the DNA binding domain suggesting that this structural change may alter the methylation target of insect Dnmt making cytosine methylation not limited to the vertebrate canonical CpG but extended to cytosine residues belonging to other dinucleotides
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