Biology Reference
In-Depth Information
(
Gaudin et al., 2001; Kotake, Takada, Nakahigashi, Ohto, & Goto, 2003;
Nakahigashi, Jasencakova, Schubert, & Goto, 2005; Turck et al., 2007
).
The role of HP1 isoforms for gene regulation during mouse preimplan-
tation development is, however, still poorly understood.
HP1b
is predom-
inantly expressed in oocytes and zygotes (
Puschendorf et al., 2008
), whereas
HP1a
appears at the 2-cell stage.
HP1g
is expressed later and throughout
development (
Meglicki, Teperek-Tkacz, & Borsuk, 2012
). Investigation
of germline knockout mutant mice for either
HP1
isoform would help us
to understand better their role, if any, for proper transcriptional regulation
during early embryo development.
2.2. Function in the germline
The germline can be viewed as the immortal lineage of cells that gives rise to
haploid gametes in sexually reproducing organisms. Germ cells undergo
numerous DNA-directed events that must be tightly coordinated and con-
trolled while these cells progress through their development. Several recent
reports indicate that members of the H3K9/HP1 pathway have important
biological functions in germline maintenance, differentiation, and possibly
in the process of meiotic silencing of unpaired chromosomes and meiotic
sex chromosome inactivation (MSCI). These last two phenomena, collec-
tively called “meiotic silencing,” target sex chromosomes in the heteroga-
metic sex (the X chromosome in male nematodes and the XY body in male
mice) and also any other chromosomes that fail to synapse due to mutation
or chromosomal rearrangement. Meiotic silencing is of crucial importance as
it is hypothesized to maintain genome integrity (
Turner, 2007; Zamudio,
Chong, & O'Bryan, 2008
). Many members of the H3K9/HP1 pathway
are highly expressed in germ cells (
Khalil, Boyar, & Driscoll, 2004; Peters
et al., 2001; van derHeijden et al., 2007
).Mouse
Suv39h2
is abundant in testes
and in oocytes compared to
Suv39h1
which is more ubiquitously expressed in
somatic tissues (
O'Carroll et al., 2000; Puschendorf et al., 2008
).
Suv39h1
/
2
DKO mice are viable, but display impaired spermatogenesis. Spermatocytes
undergo apoptosis at the pachytene stage as a consequence of incomplete
homologue pairing and synapsis defects (
Peters et al., 2001
). Interestingly,
G9a
germline conditional knockoutmales are sterile, while fertility is severely
impaired in females (
Tachibana et al., 2007
). Mutant spermatocytes fail to
progress through the pachytene stage, show defects in double-strand break
(DSB) repair, and undergo apoptosis. It can, however, not be excluded that
these defects are a consequence of misregulation of G9a target genes.
