Biology Reference
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5.2. Dynamic occupancy of the embryonic genome by histone
marks during development through the MBT
A picture of the chromatin landscape during zebrafish development through
theMBT period starts to emerge from recent chromatin immunoprecipitation
(ChIP) data and unveils clues on potential mechanisms regulating embryonic
transcription initiated upon ZGA. Initial studies have shown enrichment in
H3K4me3 and H3K27me3 from the MBT stage onwards (
Aday et al.,
2011; Lindeman, Winata, et al., 2010; Vastenhouw et al., 2010
). In line with
data from ESCs and somatic cells, H3K4me3 predominantly marks house-
keeping genes, while H3K27me3 occupies developmentally regulated genes
(
Vastenhouw et al., 2010
). Similar findings are reported in embryos of
Xenopus
(
Akkers et al., 2009
)and
Drosophila
(
Bonn et al., 2012; Schuettengruber et al.,
2009
). Interestingly, H3K27me3 occupies developmental promoters and
enhancers that are temporally and spatially controlled during early develop-
ment (
Akkers et al., 2009; Bonn et al., 2012
).
Intriguingly, occupancy of the zebrafish genome by modified histones
has initially not been evidenced by ChIP before the MBT (
Vastenhouw
et al., 2010
). This has led to the perception that the “chromatin signature
of embryonic pluripotency” is established during embryonic genome acti-
vation at the MZT (
Vastenhouw et al., 2010
). However, one would argue
that the rapid cell cycles that precede the MZT in zebrafish make it unlikely
that chromatin marks of embryonic development be established in a gene-
specific manner concomitantly with ZGA onset. Recent evidence demon-
strates occupancy of the zebrafish genome by modified histones prior to the
MBT and ZGA onset (
Lindeman et al., 2011
), suggesting an epigenetic
prepatterning of developmental gene expression before the start of embry-
onic gene expression.
Refinement of the ChIP assay for pre-MBT zebrafish embryos (a technical
challenge due to the large amount of yolk relative to cell mass and the low
nuclear-cytoplasmic ratio) has recently unveiled the marking of genes by
trimethylated H3K4, H3K9, and H3K27 at the 256-cell stage, that is, two cell
cycles before ZGA onset (
Lindeman et al., 2011
).Whether genes are also mar-
ked by modified histones at earlier stages is likely but requires further exami-
nation (Leif C. Lindeman and Philippe Collas, unpublished data). UsingChIP,
we have identified
500 by
H3K9me3, and over 1000 promoters marked by H3K4me3 at the 256-cell
stage (
Fig. 3.4
A). Corresponding genes are enriched in cellular homeostasis
and developmental functions (H3K4me3-marking), intracellular signaling
200 promoters marked by H3K27me3,
