Cell and Molecular Biology of DNA Methyltransferase 1 - International Review of Cell and Molecular Biology - page 11

for maintaining CpG methylation and CMT3 is the primary enzyme for
maintaining CpHpG methylation ( Goll and Bestor, 2005 ). MET1 was
the first plant methyltransferase to be identified ( Finnegan and Dennis,
1993; Finnegan et al., 1996; He et al., 2011; Ronemus et al., 1996 ). Geno-
mic demethylation occurs in homozygous met1 mutant plants, and this
demethylation is almost entirely at CpG dinucleotides, not CpHpG trinu-
cleotides. Interestingly, A. thaliana plants with significant downregulation of
MET1 survive with reduced levels of CpG methylation and the reduced
levels are maintained in subsequent generations even if MET1 levels are
restored ( Finnegan et al., 1996; Ronemus et al., 1996 ). In contrast, lack
of DNMT1, the only enzyme that maintains methylation on CpG dinucle-
otides in mammals, leads to certain embryonic lethality ( Li et al., 1992 ).
Different functional and/or structural motifs have been identified in the
various cytosine maintenance methyltransferases. Comparisons of amino
acid sequences among these enzymes have revealed that many, but not
all, of these motifs are shared among plant and animal DNA met-
hyltransferases. The positions of the shared and unshared motifs are shown
in Fig. 1.4 , allowing us to delineate important shared and unique aspects of
different regions of maintenance methyltransferases. A comparison of the
presence or absence of these motifs among the various maintenance met-
hyltransferases is instructive.
At the carboxy terminus of all maintenance methyltransferases are highly
conserved amino acid sequences, usually in the form of 10 typical sequence
motifs, that define important amino acids for enzyme catalysis ( Lauster et al.,
1989; Posfai et al., 1989 ). These amino acids reside in all three examples of
maintenance methyltransferases. As we move away from the carboxy termi-
nus toward the amino terminus, similarity between CMT3 and the other
two enzymes is reduced ( Fig. 1.4 ). Similarities in the amino acid sequence
between the A. thaliana MET1 and mouse DNMT1 remain, however, and it
is instructive to point out the significance of the similar motifs, as well as
motifs in DNMT1 that are no longer shared with MET1. Two bromo-
adjacent homology (BAH) domains are found in both proteins, at similar
distance from the two proteins' catalytic domains. BAH domains are present
in many distinct proteins, including the Arabidopsis CMT3 methyltransferase
enzyme, and are often associated with biological processes involving physical
interactions between two proteins, chromatin structure, and particularly
association of genomic DNA with nucleosomes ( Callebaut et al., 1999 ).
Both MET1 and DNMT1 have significant amino acid sequence similar-
ity (

25%) N-terminal of their BAH1 and BAH2 domains, yet interestingly