Biomedical Engineering Reference
In-Depth Information
function only (Goll et al.
2006
; Jurkowski et al.
2008
), and DNMT3L protein lacks
a catalytic domain; however, it acts as a positive regulator of DNMT3A (Chedin
et al.
2002
). This epigenetic modifi cation mainly occurs in a simple dinucleotide
cite, CpG. Depending on the organism, roughly 60-90 % of all CpG dinucleotides
in mammals are methylated. Most methylated CpGs are scattered throughout the
genome preventing transcription or transposition of retroviral elements. However,
some are clustered in regions of relatively high CpG density known as “CpG
islands.” These are usually between 200 and 500 bp in size, often cover the pro-
moter region of genes, and are kept methylation free. Locally, methylation of cyto-
sine residues is the most common epigenetic modifi cation of mammalian genomic
DNA and is primarily associated with transcriptional regulation of tissue-specifi cally
expressed genes or silencing of tumor suppressor genes in cancer cells (Novak et al.
2006
), stem cells (Rodic et al.
2005
) and glial cells (Hoffman and Hu
2006
).
Methylated cytosine residues are not only found in vertebrates but also in inverte-
brates, such as chordates (Simmen et al.
1999
; Suzuki et al.
2007
), echinoderms
(Tweedie et al.
1997
), and insects (Field et al.
2004
; Glastad et al.
2011
; Lyko and
Maleszka
2011
).
Especially in insects,
Drosophila melanogaster
is the most studied invertebrate
species in the fi eld of DNA methylation.
Drosophila
DNA methyltransferase
(dDNMT2), which is closely related to the mammalian DNMT2 family and is
encoded by a single DNA methyltransferase gene in the
Drosophila
genome
(Tweedie et al.
1999
; Hung et al.
1999
; Tang et al.
2003
; Marhold et al.
2004
),
putatively methylated the components of retrotransposons and repetitive DNA
sequences (Salzberg et al.
2004
). Overexpression of dDNMT2 resulted in signifi -
cant genomic hypermethylation at CpT and CpA dinucleotides, but not CpG dinu-
cleotides (Kunert et al.
2003
). In addition, the
Drosophila
genome contains a single
gene that encodes a methyl-CpG-binding domain protein (MBD2/3) with extensive
homology to the vertebrate methyl-DNA binding proteins MBD2 and MBD3
(Tweedie et al.
1999
; Roder et al.
2000
; Ballester et al.
2001
). Band shift assays
have demonstrated the specifi c binding of MBD2/3 to CpT/A-methylated DNA
(Marhold et al.
2004
), which refl ects the endogenous DNA methylation pattern in
Drosophila
(Lyko et al.
2000
).
10.2
Honeybee as a Model Organism for Epigenetic Analyses
In this review, we focused on the honeybee
Apis mellifera
as a model organism for
epigenetic analyses. The honeybee is an excellent model organism for understand-
ing the relationship between behavioral changes and epigenetic modifi cations for
several reasons. First, the entire genome sequencing of honeybee has been com-
pleted, which is essential for the comprehensive understanding of epigenetic
modifi cation systems (The Honeybee Genome Sequencing Consortium
2006
;
