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that dSETDB1 regulates both germ cell maintenance and differentiation. It
has been proposed that dSETDB1 and
SU(VAR)3
-
9
cooperate during germ
cell maturation. As germ cells mature and differentiate,
dSETDB1
expression
decreases and its function is gradually taken over by
Su
(
var
)
3
-
9
(
Yoon et al.,
2008
). Some interplay between these two H3K9 KMTs is reinforced by the
fact that the
dSETDB1
mutant phenotype is less severe in
Su
(
var
)
3
-
9
-deficient
flies (
Brower-Toland, Riddle, Jiang, Huisinga, & Elgin, 2009; Seum,
Bontron, et al., 2007; Seum, Reo, et al., 2007
). This puzzling phenotypic
connection remains unresolved at the molecular level. In mammals, the
exact function of SETDB1 in the germline is unknown and possible links
between the different H3K9 KMT enzymes are not clear either. One study
even suggested that Suv39h1, G9a, Glp, and SETDB1 are part of the same
complex (
Fritsch et al., 2010
). However, since these enzymes show different
expression pattern during development, the molecular composition and
function of such putative H3K9 methylation complex is still an open question
(
Box 8.2
).
Recently, PRDM3/16 were characterized as H3K9me1 KMTs that
provide a template for Suv39-mediated H3K9me3 conversion at PCH
(
Pinheiro et al., 2012
). Importantly, these proteins are essential for the clus-
tering of pericentromeric regions into chromocenters. Although using dif-
ferent enzymes, this pathway seems to be by largely conserved in
C. elegans
,
where it is required for maintenance of the anchoring of heterochromatic
regions to the nuclear periphery (
Towbin et al., 2012
). The role of these
enzymes, during germline and early embryonic development awaits further
investigations.
2.3. New insights into the function of H3K9/HP1 pathway?
During the past decade, we gathered a better understanding of the function
of H3K9 KMT and HP1 proteins. Although many points need further
investigation, knockout and knockdown studies in various organisms
allowed us to appreciate more their role for proper development. However,
most of these experiments focus on the catalytic activity of KMT toward
histones. Since its discovery, methylation of proteins involves many different
substrates (
Paik, Paik, & Kim, 2007
). For instance, G9a has substrates other
than the canonical histones (
Chin et al., 2007; Sampath et al., 2007
). There-
fore, identification of nonhistone substrates for the other H3K9 KMTwould
be of great interest, as PTMs of proteins could lead to a variety of biological
outputs.
