Biology Reference
In-Depth Information
multiple roles during development and serves to establish long-term gene silencing. In
2009, it was revealed that 5-hydroxymethylcytosine (5hmC) is another prominent cyto-
sine modification catalyzed by the enzymes of the TET family and abundant in certain
cell types. 5hmC has been thought to serve as an intermediate in the reaction of DNA
demethylation or act as a signal for chromatin factors. Here, we review the current
knowledge on the roles of these DNA epigenetic marks in development, epigenetic
reprogramming, and pluripotency.
1. INTRODUCTION
“Epigenetics” defines the processes that ensure the propagation of phe-
notypes through mitosis or meiosis without irreversible changes in the genetic
sequence (
Berger, Kouzarides, Shiekhattar, & Shilatifard, 2009
). This epige-
netic information can reside in posttranslational modifications of histones and
cytosine modifications, which modify the accessibility of the DNA and pro-
vide recognition motifs for chromatin-binding proteins. When inherited dur-
ing cell division, these marks provide a memory of gene expression states that
is crucial to maintain cellular identity. During development, these epigenetic
marks undergo global changes that contribute to the restriction of cellular
potential and the formation of distinct cell lineages (
Meissner, 2010
).
The most abundant epigenetic mark of DNA is methylation of the carbon
5 of cytosines (
Fig. 2.1
A), which creates 5-methylcytosine (5mC). 5mC is
abundant in vertebrates and occurs almost exclusively as a symmetrical mark
at CpG dinucleotides (
Fig. 2.1
B). It is also found in invertebrate species, albeit
at lower levels than in vertebrate genomes (
Suzuki & Bird, 2008
). Cytosine
methylation is catalyzed by DNAmethyltransferases (DNMTs) that methylate
DNA
de novo
during development and propagate DNA methylation during
replication (
Fig. 2.1
B). While initially viewed as a repressive mark, the recent
progress in genome-wide mapping sheds new light on the complex relation-
ship between DNA methylation and gene expression.
5-Hydroxymethylcytosine (5hmC), another modified base present in
vertebrate DNA (
Fig. 2.1
A;
Penn, Suwalski, O'Riley, Bojanowski, &
Yura, 1972
), was recently found to be catalyzed by the enzymes of the
ten-eleven translocation (TET) family and to be relatively abundant in plu-
ripotent cells and neurons (
Kriaucionis & Heintz, 2009; Tahiliani et al.,
2009
). With the parallel discovery that TET2 is mutated in a large fraction
of myeloid malignancies (
Abdel-Wahab et al., 2009; Delhommeau et al.,
2009; Langemeijer et al., 2009
), this groundbreaking discovery led to the
