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changing the components of the complex can dramatically alter the
enzymatic activity of Sce. In fact, the discovery of the Polycomb repressive
deubiquitinase complex “PR-DUB” revealed that the ubiquitination
activity of dRAF/PRC1 needs to be counterbalanced in order to prevent
repression of unintended targets ( Scheuermann et al., 2010 ). PR-DUB
consists of the deubiquitinating enzyme Calypso and the PcG protein
ASX that co-occupy Polycomb target genes. The functional combination
of dRAF and PR-DUB allows precise regulation of the dosage of Polycomb
repression ( Scheuermann et al., 2010 ). Genetic, genome-wide expression,
and chromatin analyses further show that SCE, PSC, and PR-DUB, regu-
lating H2A monoubiquitination levels, are only required for repression of a
subset of PRC1 target genes. Repression of other targets depends on the
function of the PSC paralog Su(z)2 and the Ph protein, possibly by medi-
ating chromatin compaction ( Guti´rrez et al., 2012 ).
3.1.2.2 Mammals
The PRC1members inmammals have undergonemultiple duplications dur-
ing evolution, and there are six homologues of Drosophila Psc ( Pcgf1 / 2 / 3 / 4 /
5 / 6 ), five homologues of Pc ( Cbx2 / 4 / 6 / 7 / 8 ), three homologues of Ph ( Phc1 /
2 / 3 ), and two homologues of Sce ( Ring1 / Rnf2 ). The only gene that has been
shown to be embryonic lethal at early postimplantation is Rnf2 (see Table 8.3 ),
while Pcgf2 , Pcgf4 , Cbx2 , and Phc1 show perinatal lethality and/or homeotic
transformations ( Akasaka et al., 1996; Cor ´ et al., 1997; Katoh-Fukui et al.,
1998; Takihara et al., 1997; van der Lugt et al., 1994 ). Phc2 and Ring1 mutant
mice are healthy and fertile with minor homeotic transformations in the
anterior-posterior axis ( del Mar Lorente et al., 2000; Isono et al., 2005 ). Fur-
thermore, two studies analyzing the role of Cbx2 point to a function of PRC1
in sex determination and meiotic regulation ( Baumann & De La Fuente,
2011; Katoh-Fukui et al., 1998 ). The fact that only Rnf2 is indispensable
for embryonic development could be explained with the presence of redun-
dant paralogs. This is evident from several studies of DKOmice, which show
dramatically enhanced phenotypes compared to the single mutations. In the
first study, Akasaka and colleagues showed that double deficiency for Pcgf2
and Pcgf4 results in postimplantation lethality during somite formation and
organogenesis as a result of misregulated Hox gene expression ( Akasaka
et al., 2001 ). In another study, Posfai and colleagues removed both Ring1
and Rnf2 in the female germline and observed a strong maternal effect
leading to a 2-cell embryonic arrest, that is, the stage before zygotic genome
activation ( Posfai et al., 2012 ). The authors profiled the transcriptome of
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