Biology Reference
In-Depth Information
Ring1
/
Rnf2
-deficient fully-grown oocytes and revealed massive gene
misregulation. Furthermore, they presented evidence that Ring1/Rnf2 are
responsible for global H2AK119 ubiquitination inmammalian oocytes.With
a similar genetic approach, Lapthanasupkul et al. examined the function of
Ring1
and
Rnf2
in mesenchymal stem cells and revealed that upon DKO,
the proliferation of the stem cells and the differentiation process are severely
affected (
Lapthanasupkul et al., 2012
). A number of developmental regulator
genes that show a restricted expression pattern in normal tissue were broadly
expressed in the mutant tissue. Interestingly, these authors reported that the
removal of Ring1/Rnf2 resulted in a massive depletion of Kdm2b protein.
The latter has been identified as a member of the human BCOR complex,
which is the homologue of dRAF (
Gearhart, Corcoran, Wamstad, &
Bardwell, 2006
). It remains tobe shownwhethermammalianBCORhas spe-
cialized as the major H2AK119 ubiquitin ligase and whether the H3K36
demethylase activity is coupled to Polycomb-mediated repression. A hint
into this direction presents the recently published large-scale genomics data
from the human ENCODE project, which shows that H3K27me3 and
H3K36me3 are largely mutually exclusive (
Consortium T.E.P., 2012;
Voigt et al., 2012
). The study that identified the fly PR-DUB complex also
showed that the human homologues of
Calypso
and
ASX
(
BAP1
and
Asxl1
,
respectively) form a complex and have deubiquitinase activity
in vitro
,
suggesting a conserved molecular function for this Polycomb-related
complex (
Scheuermann et al., 2010
). Indeed, homozygous
Asxl1
-deficient
mice have homeotic transformations and die shortly after birth (
Fisher
et al., 2010
). Finally, Gao and colleagues addressed the variety of mammalian
PRC1-like complexes in a systematic way and identified four major PRC1
subtypes, which differ by the presence of different Pcgf and Cbx homologues
and target sequences (
Gao et al., 2012
). Tavares and colleagues identified
another PRC1 complex containing RYBP, Rnf2, and Mel18/Pcgf2 that
is highly catalytically active and is targeted to chromatin in an unknownman-
ner, independently of
Eed
function and H3K27me3 (
Tavares et al., 2012
).
Rybp
is essential for gastrulation (
Pirity, Locker, & Schreiber-Agus, 2005
)
and
in vitro
differentiation of ESCs. Rybp is not required for self-renewal
of ESCs and mediates repression of certain endogenous retroviruses and
preimplantation and germline genes (
Hisada et al., 2012
). The extensive
variety in complexes potentially underlies different biological roles in specific
developmental contexts. To address this issue, future studies will have to
target individual Pcgf, Cbx, and Rybp/Yaf2 components rather than the
common Ring1 and Rnf2.
