ISSN 1022-7954, Russian Journal of Genetics, 2006, Vol. 42, No. 9, pp. 985–997. © Pleiades Publishing, Inc., 2006.
Original Russian Text © B.F. Vanyushin, 2006, published in Genetika, 2006, Vol. 42, No. 9, pp. 1186–1199.
Fifty years ago, professor of the Department of
Plant Biochemistry, Faculty of Biology and Soil Sci-
ence of Moscow State University, Andrei Nikolaevich
Belozersky, recruited me, the fourth-year student of the
same department, to study nucleic acids. I was respon-
sible for analysis of DNA and RNA nucleotide compo-
sition in some bacteria. Analysis of bacterial DNA
composition, performed at that unforgettable time,
clearly showed that the DNA CG content was species-
speciﬁc and could serve as an important taxonomic
character in bacteria . In fact, this work was among
those, which formed the basis of gene systematics. At
that time, the world of eukaryotic DNA was practically
undiscovered. For instance, the data on the DNA com-
position in the whole plant kingdom were restricted to
wheat embryonic DNA; among fungi these were the
data on yeast DNA; and in animals the data were repre-
sented by those for calf thymus DNA and for the DNA
from rat spleen (liver). Nevertheless, at that time it had
been already established that some DNAs in addition to
ordinary bases (A, G, C, and T), could contain the
minor base, 5-methylcytosine (m
C) [2, 3]. Later on, in
A) was discovered .
For a long time, the origin of these DNA bases
remained unknown. Only in 1963, speciﬁc enzymes
capable of selective and speciﬁc methylation of certain
cytosine and adenine residues in the DNA strands in the
presence of the methyl group donor, S-adenosyl-L-
methionine (SAM or AdoMet), were ﬁrst described in
bacteria and then in eukaryotes . It became clear that
“minor” bases detected in the DNA molecule (m
A) did not incorporate into DNA in the ready-made
form, but appeared as a result of enzymatic modiﬁca-
tion (methylation) of the corresponding ordinary bases
in the forming, or the already formed DNA strands.
However, speciﬁcity and functional role of enzymatic
DNA methylation remained unclear.
Moreover, the idea that these “minor” bases did not
play any important role in the DNA structure and func-
tioning was very popular. Classical object of traditional
DNA Methylation and Epigenetics
B. F. Vanyushin
Belozersky Institute of Physical and Chemical Biology, Moscow State University, Moscow, 199992 Russia;
fax: 7(495)939-31-81; e-mail: firstname.lastname@example.org
Received February 15, 2006
Methylation helps life, and it can take it away.
Actually, without methylation life would be absolutely impossible.
—In eukaryotic cells, nuclear DNA is subject to enzymatic methylation with the formation of 5-meth-
ylcytosine residues, mostly within the CG and CNG sequences. In plants and animals this DNA methylation is
species-, tissue-, and organelle-speciﬁc. It changes (decreases) with age and is regulated by hormones. On the
other hand, genome methylation can control hormonal signal. Replicative and post-replicative DNA methyla-
tion types are distinguished. They are mediated by multiple DNA methyltransferases with different site-speci-
ﬁcity. Replication is accompanied by the appearance of hemimethylated DNA sites. Pronounced asymmetry of
the DNA strand methylation disappears to the end of the cell cycle. A model of methylation-regulated DNA
replication is proposed. DNA methylation controls all genetic processes in the cell (replication, transcription,
DNA repair, recombination, and gene transposition). It is the mechanism of cell differentiation, gene discrimi-
nation and silencing. In animals, suppression of DNA methylation stops development (embryogenesis),
switches on apoptosis, and is usually lethal. Disruption of DNA methylation pattern results in the malignant cell
transformation and serves as one of the early diagnostic features of carcinogenesis. In malignant cell the pattern
of DNA methylation, as well as the set of DNA methyltransferase activities, differs from that in normal cell. In
plants inhibition of DNA methylation is accompanied by the induction of seed storage and ﬂorescence genes.
In eukaryotes one and the same gene can be simultaneously methylated both at cytosine and adenine residues.
It can be thus suggested, that the plant cell contains at least two different, and probably, interdependent systems
of DNA methylation. The ﬁrst eukaryotic adenine DNA methyltransferase was isolated from plants. This
enzyme methylates DNA with the formation of N
-methyladenine residues in the sequence TGATCA
. Plants possess AdoMet-dependent endonucleases sensitive to DNA methyla-
tion. It seems likely that plants, similarly to microorganisms and some lower eukaryotes, have restriction–mod-
iﬁcation (R–M) system. Discovery of the essential role of DNA methylation in regulation of genetic processes
served as a principle basis and materialization of epigenetics and epigenomics.