Biology Reference
In-Depth Information
BOX 8.2 Removal of H3K9 methylation by KDMs during
germ-cell development
The balance between establishment and erasure of H3K9 methylation is also cru-
cial for proper embryo development. The expression of the H3K9me1/2 JmjC-
domain-containing histone demethylase 2a (Jhdm2a) enzyme partially overlaps
with that of G9a, whereas G9a is continuously expressed in the germline until
its downregulation during meiotic prophase, and Jhdm2a is found transcribed
from late pachytene onward, with high expression levels in round and elongating
spermatids (
Okada, Tateishi, & Zhang, 2010
). Although Jhdm2a knockout mice are
viable, they display smaller testis, infertility, and obesity (
Okada, Scott, Ray,
Mishina, & Zhang, 2007, Okada et al., 2010
). Disruption of this enzyme causes
defects in postmeiotic chromatin condensation in elongating spermatids leading
to impaired nuclear elongation. Interestingly, Jhdm2a was shown to bind to the
promoter region of genes encoding Transition Protein 1 (Tnp1) and Protamine 1
(Prm1). Tnp1 and Prm1 are required for correct nuclear condensation during sper-
miogenesis (
Cho et al., 2001; Zhao et al., 2004
). Furthermore, deficiency for
Jhdm2a impairs transcriptional activation of Tnp1 and Prm1 leading to infertility
(
Okada et al., 2010
). Interestingly, the four members of the Jmjd2 family of KDMs in
mammals show dual specificity for the removal of H3K9me3/2 and H3K36me3/2
in vitro (
Fodor et al., 2006; Klose, Kallin, & Zhang, 2006; Whetstine et al., 2006
).
RNAi depletion of the C. elegans homologue jmjd-2 induces increased levels of
H3K9me3 (and H3K36me3 on one end of the X chromosome) in the germline.
Germ cells depleted for jmjd-2 showed increased apoptosis and altered DSB
repair although they do not harbor defects in pairing and synapsis (
Whetstine
et al., 2006
). This dynamic interplay between the deposition and the erasure of
H3K9 methylation is reinforced by the fact that the phenotype of jmjd-2
/
ani-
mals can be partially rescued by the deletion of HPL-2, the C. elegans homologue
of HP1 (
Black et al., 2010
).
Indeed, HP1 is dynamically posttranslationally modified, which can
affect its localization toward PCH (
Maison et al., 2011
) or following
DNA damage (
Ayoub, Jeyasekharan, Bernal, & Venkitaraman, 2008;
Dinant & Luijsterburg, 2009
). Moreover, the different HP1 isoforms do
not show similar localization, associate with different proteins, and harbor
noncompletely redundant functions in various organisms. Thus, HP1
isoforms and their PTMs may constitute additional layer of information,
increasing the complexity of genome control by chromatin-modifying
enzymes.
