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seem to constitute a platform for trimethylation of H3K4 (H3K4me3;
Thomson et al., 2010
), a transcriptionally permissive modification, prior to
ZGA (
Andersen, Reiner, et al., 2012
;
Fig. 3.3
B). In contrast, trimethylation
of H3K9 (or H3K27me3), associated with transcriptional repression,
mainly occurs on methylated promoters (
Andersen, Reiner, et al., 2012
;
Fig. 3.3
B). As discussed below, H3K4me3 on hypomethylated developmen-
tally regulated promoters pre-MBT is strongly suggestive of gene expression
potential after ZGA onset (
Lindeman et al., 2011
).
Where does the hypomethylated state come from? A significant fraction
of genes hypomethylated in pre-MBT embryos are also hypomethylated in
sperm (
Andersen, Reiner, et al., 2012; Wu, Zhang, &Cairns, 2011
). Indeed,
although sperm exhibits DNA methylation levels comparable to those of
somatic cells (
Wu, Zhang, & Cairns, 2011
), both sperm and embryos are
marked by regions of methylation and hypomethylation. Hypomethylated
genes in sperm and embryos encode for the most part developmentally
regulated transcription factors, and hypomethylation occurs either on
stand-alone genes or over entire clusters (e.g.,
hox
loci;
Fig. 3.3
A;
Andersen, Reiner, et al., 2012; Wu, Zhang, & Cairns, 2011
). This suggests
that hypomethylation may confer, already in sperm, an instructive role for
developmental gene expression. Likewise, the hypomethylated state of
maternally expressed genes with cellular homeostatic (housekeeping) func-
tions (
Aanes et al., 2011
) lends support to the view of an instructive function
of promoter hypomethylation also in egg. We recently proposed that one
such instructive function may be H3K4 trimethylation (
Andersen,
Reiner, et al., 2012
). Because DNA methylation functionally interacts with
histone modifications (
Bannister & Kouzarides, 2011; Fuks, 2005; Fuks,
Hurd, Deplus, & Kouzarides, 2003; Rai et al., 2006
; see also below), it
emerges from these studies that a role of DNA methylation in the regulation
of ZGAmay be the priming of chromatin states, prior to ZGA, for transcrip-
tional competence by association with modified histones.
5. PREPATTERNING DEVELOPMENTAL GENE
EXPRESSION BY MODIFIED HISTONES BEFORE ZGA
5.1. Histone methylation marks of promoters and
enhancers
The second class of epigenetic changes that accompany development
through the ZGA period involves the posttranslational modifications of his-
tones. These changes occur predominantly in regions of developmental
importance, encompassing housekeeping, and developmentally regulated
