Overview of Mammalian Genome special issue on epigenetics
Received: 1 October 2009 / Accepted: 1 October 2009 / Published online: 28 October 2009
Ó Springer Science+Business Media, LLC 2009
In 1942 C.H. Waddington devised the term ‘‘epigenetics’’
to describe the causal mechanisms of development from
the fertilised egg to adult (Waddington 1942). In broad
terms this deﬁnition still holds, but with time, and
increasing knowledge, the term ‘‘epigenetics’’ now covers
the study of heritable chromatin modiﬁcations that regulate
gene expression but do not alter DNA sequence. These
modiﬁcations comprise modiﬁcations of histone proteins
and DNA, epigenetic marks that are heritable in mitotically
dividing cells. Epigenetic marks are key to fundamental
developmental processes of differentiation, X chromosome
inactivation, and genomic imprinting. Aberrant epigenetic
marks are associated with developmental disorders and,
increasingly, with diseases that manifest in adults.
The main topics covered in this special issue of Mam-
malian Genome are genomic imprinting and the role of
epigenetics in disease. However, one of the earliest epige-
netic phenomena to be studied in mammals was X chromo-
some inactivation whereby one of the two X chromosomes in
females is silenced. In this issue Shevchenko et al. describe a
cytogenetic analysis of epigenetic marks on the inactive X
(Xi) of the vole Microtus rossiaemeridionalis and found both
similarities and differences when compared with the more
widely studied mouse and human Xi.
Genomic imprinting was recognised in the mid-1980s in
mouse nuclear transplantation and genetic experiments
(Cattanach and Kirk 1985; McGrath and Solter 1984;
Surani et al. 1984). The nuclear transplantation experi-
ments showed that parental genomes must be marked or
imprinted during parental gametogenesis to function dif-
ferently in the zygote, and the genetic experiments showed
that it was only speciﬁc regions of certain chromosomes,
implying speciﬁc genes, that were so imprinted. The ﬁrst
imprinted genes were discovered in 1991 (Barlow et al.
1991; DeChiara et al. 1991) and now about 100 are known
in Eutherian mammals (Williamson et al. 2009). These
genes are expressed according to parental origin, with
expression controlled by epigenetic marks.
Imprinted genes tend to be arranged in clusters, ranging
in size from less than 100 kb to over 1 Mb. Tierling et al.
show that the gene Begain marks the proximal boundary of
the cluster of imprinted genes on mouse chromosome 12,
and extends the size of the cluster by 600 kb.
A master regulator, the imprinting centre, controls
parental speciﬁc gene expression within a cluster. All
imprinting centres are marked by differential methylation
according to parental origin, and there has been consider-
able progress in understanding how these marks are
established in the germline and subsequently maintained.
More recently, differential histone modiﬁcations have been
described at imprinting centres and the intimate links
between DNA methylation, histone methylation, and non-
histone proteins are just starting to be understood. In this
issue Weaver et al. and Feil and Kacem review epigenetic
changes in development associated with imprinting.
However, we have limited understanding of the mecha-
nisms whereby the methylation machinery is targeted to
imprinting centres, although new data show that demeth-
ylation of histones is a necessary ﬁrst step (Ciccone et al.
2009). The target for DNA methylation is CpG, a dinu-
cleotide that tends to occur in clusters called CpG islands
J. Peters (&)
Mammalian Genetics Unit, MRC Harwell, Harwell Science
and Innovation Campus, Oxfordshire OX11 0RD, UK
Mamm Genome (2009) 20:529–531