H3K9/HP1 and Polycomb: Two Key Epigenetic Silencing Pathways for Gene Regulation and Embryo Development - Current Topics in Developmental Biology - page 247

BOX 8.1 Interplay between H3K9 and DNA methylation cont'd

which binds to H3K9me3 through its CD and to DIM-2 through its CSD ( Honda &
Selker, 2008 ). Mutation of the N. crassa HP1 gene, hpo, results in severe defects of
DNA methylation without altering H3K9me3, like DIM-2 mutants ( Freitag, Hickey,
Khlafallah, Read, & Selker, 2004 ). Strikingly, this suggests that DIM-5 and HP1 are
upstream of DNA methylation in N. crassa. Moreover, H3K9me3, HP1, and DNA
methylation colocalize almost perfectly on 44 defined heterochromatic domains
on linkage group VII ( Lewis et al., 2009 ). Interestingly, HP1 also prevents the
spreading of heterochromatic domains by association with the jmjC domain con-
taining KDM DMM-1/2 (DNA methylation modulator 1/2). DMM-1/2 removes
H3K9me3 and then prevents further accumulation of HP1 and DNA methylation
( Honda et al., 2010 ). Similarly, such antisilencing mechanisms also exist in
S. pombe and A. thaliana ( Miura et al., 2009; Saze, Shiraishi, Miura, & Kakutani,
2008; Zofall & Grewal, 2006 ). In the yeast S. pombe, there is clear evidence of
the role played by the RNAi pathway in recruitment of the H3K9me3 KMT Clr4
and heterochromatin formation ( Zhang, Mosch, Fischle, & Grewal, 2008 )
(although it lacks DNA methylation) and to a lesser extend in plants and Drosoph-
ila from the RNA-directed DNA methylation (RdDM) ( Law & Jacobsen, 2010 ) and
the piRNAs pathway, respectively ( Pal-Bhadra et al., 2004 ). In N. crassa, targeting
of DIM-5 to chromatin relies on its interaction with another factor, DIM-7 ( Lewis,
Adhvaryu, Honda, Shiver, & Selker, 2010 ). Therefore, despite the differences
between the model organisms cited so far, it seems that methylation of DNA
and H3K9 cooperate for mediating chromatin silencing.

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development of flowering organs ( Jackson et al., 2002; Yun, Weigel, & Lee,
2002 ). However, the principal role of plant Su(var)3-9 homologues SUVH
and SUVR seems to be the control of transposons in heterochromatin dur-
ing plant development ( Kuhlmann & Mette, 2012; Naumann et al., 2005;
Thorstensen, Grini, & Aalen, 2011 ).

2.1.2 SETDB1
During mouse preimplantation development, transcriptional regulation
seems to rely more on other classes of the H3K9 KMT including G9a
and ESET/SETDB1 and on the H3K9 KDMs of the JMJD2 family. Indeed,
murine ESCs inactivated for Setdb1 or the two KDM Jmjd2a and
Jmjd2c are unable to maintain self-renewal and differentiate ( Loh,
Zhang, Chen, George, & Ng, 2007 ). SETDB1 associates with the core
pluripotency transcription factor Oct3/4 and regulates a specific set of devel-
opmental genes, most of

them related to the trophectoderm lineage