Biology Reference
In-Depth Information
patterns in both the soma and the germline begins with global methylation of non
CpG island sequences in the embryo whilst the final methylation patterns are
determined by a specific and highly regulated process of demethylation (Razin
and Shemer, 1995).
In humans, differences in site-specific methylation patterns between different
ethnic groups have not so far been apparent in studies of a variety of different
types of DNA sequence (Behn-Krappa
et al
., 1991; Bottema
et al
., 1990; Kochanek
et al
., 1990). In keeping with these reports, Millar
et al
. (1998) found no evidence
in sperm DNA for variable methylation status in the factor VIII (
F8C
; Xq28)
gene between European Caucasians and Asians. However, the methylation status
of specific CpG sites in the
F8C
gene did exhibit significant inter-individual vari-
ation (Millar
et al
., 1998).
CpG islands.
Spatially, the distribution of CpG appears to be nonrandom in
the human genome; about 1% of the genome consists of stretches very rich in
CpG which together account for roughly 15% of all CpG dinucleotides (Bird,
1986). In contrast to most of the scattered CpG dinucleotides, these
CpG islands
represent unmethylated domains and comprise ~50% of all unmethylated
CpGs in the genome (Bird
et al
., 1985). CpG islands occur, on average, every
100 kilobases in the murine genome (Brown and Bird, 1986) and, in human, are
often located immediately 5
to gene coding regions (Gardiner
et al
., 1990;
Larsen
et al
., 1992;
Figure 1.6
). The methylation of CpG islands may modulate
gene expression through its influence on chromatin organization (Kundu and
Rao, 1999).
Not all vertebrate genes, however, possess CpG islands (Bird, 1986;
Gardiner-Garden and Frommer, 1987;
Figure 1.6
) and many are partially or
even heavily methylated. In general, gene promoters containing CpG islands
are unmethylated regardless of expression whereas promoters lacking CpG
(a)
CpG island - unmethylated
5'
3'
CpG/GpC = 1
CpG/GpC = 0.2
(b)
Promoter
5'
3'
CpG/GpC = 0.2
Figure 1.6.
The distribution of CpG within genes. (a) A typical CpG island containing
gene as found in many 'housekeeping' genes. (b) A typical tissue-specific gene lacking a
CpG island.
