Biology Reference
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in the embryo, which is referred to as compaction and is achieved through the
establishment of E-cadherin junctions at the end of the 8-cell stage.
Regarding the histone methyltransferases that catalyze the methylation of
H3K9 and H4K20, many of them have been zygotically knocked-out in the
mouse and some of them have early embryonic phenotypes (
Table 1.1
). In
contrast, the methyltransferase(s) responsible for H3K64me3 have not been
identified so far. At least eight proteins (Suv39h1, Suv39h2, G9a/Ehmt2,
Eset/Setdb1, EuHMTase/GLP, Kmt1d, CLL8, SpClr4) have been described
to methylate H3K9 (
Kouzarides, 2007
), and the list has been recently
expanded to 10, as monomethyltransferase activity toward H3K9 has been
observed for Prdm3 andPrdm16 (
Pinheiro et al., 2012
). The first five enzymes
are active in mammalian cells (
Dodge et al., 2004; Kouzarides, 2007
). G9a is
responsible for the mono- and dimethylation of H3K9 in euchromatic
regions (
Rice et al., 2003; Tachibana et al., 2002, 2005
). Eset is responsible
for the trimethylation of H3K9me3 in euchromatin (
Wang et al., 2003;
Yang et al., 2002
), whereas EuHMTase promotes H3K9 dimethylation of
the same regions. In contrast, Suv39h1/h2 can di- and trimethylate H3K9
in pericentric, centromeric, and telomeric regions (
Peters et al., 2001; Rea
et al., 2000
). A key downstream “reader” of H3K9me3 is the heterochroma-
tin protein 1 (HP1) (
Bannister et al., 2001; Lachner, O'Carroll, Rea,
Mechtler, & Jenuwein, 2001
), which specifically recognizes H3K9me3
through its chromodomain. HP1 has been shown in turn to recruit the
H4K20 methyltransferase Suv4-20 via its chromoshadow domain (
Nielsen
et al., 2001; Schotta et al., 2004
). Suv4-20 would subsequently establish
di- and trimethylation of H4K20me1, the latter being catalyzed by PR-
Set7 (
Nishioka et al., 2002; Schotta et al., 2004, 2008
). These steps have been
shown to operate in somatic cells to establish a constitutive heterochromatic
configuration over the specific genomic regions (
Rea et al., 2000; Schotta
et al., 2004, 2008
). The presence of H3K9me3 and H4K20me3 is character-
istic of maternal centromeric and pericentromeric regions in the zygote,
which are organized in a ring-like shape around the nucleolar-like bodies
(NLBs). It has been shown recently that another mark is present on these
regions: H3K64me3 (
Daujat et al., 2009
). However, themechanismof estab-
lishment of this modification seems to be independent from the one that we
described earlier (Lange et al., submitted for publication). Therefore, more
work should be done in order to identify the role and effect of this histone
mark during development.
A recent study has shown that a novel methyltransferase, Smyd5, can
trimethylate H4K20. It was shown that the trimethylation established by this
