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promoters are occupied by RNAPII which is restricted to the TSS and is
therefore not elongating (an example is shown in
Fig. 3.4
B). Thus,
H3K4me3 occupancy of promoters in pre-MBT embryos argues for a role
on transcription that is not merely regulatory. Indeed, examination of the
post-ZGA expression status of genes premarked by H3K4me3 before
ZGA shows that these have a greater propensity to be expressed than all
RefSeq genes activated at that time; further, expression level of these genes
is higher than that of all RefSeq activated genes (
Lindeman et al., 2011
).
These genes logically retain H3K4me3 at the TSS and acquire both
H3K36me3 and RNAPII on gene bodies. These findings strongly suggest
that H3K4me3 marking prior to ZGA generates a chromatin state permis-
sive for transcriptional activation after ZGA, and this in the absence of on-
going transcription. Affinity of H3K4me3 for hypomethylated regions
(
Andersen, Reiner, et al., 2012
) reinforces the state of transcriptional
permissiveness of this chromatin state. These data raise the view of epige-
netic prepatterning of developmental transcription program by selective
H3K4me3 marking of housekeeping and developmentally regulated pro-
moters prior to ZGA, and suggest a predictive role of H3K4me3 for devel-
opmental gene expression.
The concept of prepatterning of embryonic gene expression is gradually
emerging from several studies. Determinant of this prepatterning may be
histone modifications such as H3 methylation as described above
(
Lindeman et al., 2011
) and H4 acetylation (
Toyama, Rebbert, Dey,
Ozato, & Dawid, 2008
). Exciting recent findings also suggest that other
determinants to developmental transcription may be “stand-by” transcrip-
tion factors. The binding of factors such as Zelda, STAT92E, or
b
-catenin
to DNA has been shown to be temporally uncoupled from transcription ini-
tiation of their target genes in
Drosophila
and
Xenopus
(
Blythe, Cha,
Tadjuidje, Heasman, & Klein, 2010; Harrison, Li, Kaplan, Botchan, &
Eisen, 2011; Tsurumi et al., 2011
); they may thus preestablish gene expres-
sion potential in a spatio-temporal manner in the embryo. Similarly, in
zebrafish, H4 acetylation prior to ZGA mediates binding of the Brd4 tran-
scription factor on genes activated after ZGA onset (
Dey, Chitsaz, Abbasi,
Misteli, & Ozato, 2003; Toyama et al., 2008
); thus, histone marks may
premark genes for subsequent transcription factor binding and transcription
initiation upon ZGA. The role of transcription factors in the regulation of
ZGA and their potential function as determinants of embryonic gene acti-
vation has been recently discussed (
strup et al., 2012
). Lastly, DNA motifs
directing transcription factor binding may also represent determinants of the
