Stage-specific histone modification profiles reveal global transitions in the Xenopus embryonic epigenome.

Vertebrate embryos are derived from a transitory pool of
pluripotent cells. By the process of embryonic induction, these
precursor cells are assigned to specific fates and differentiation
programs. Histone post-translational modifications are thought to
play a key role in the establishment and maintenance of stable gene
expression patterns underlying these processes. While on gene level
histone modifications are known to change during differentiation,
very little is known about the quantitative fluctuations in bulk
histone modifications during development. To investigate this issue
we analysed histones isolated from four different developmental
stages of Xenopus laevis by mass spectrometry. In toto, we
quantified 59 modification states on core histones H3 and H4 from
blastula to tadpole stages. During this developmental period, we
observed in general an increase in the unmodified states, and a
shift from histone modifications associated with transcriptional
activity to transcriptionally repressive histone marks. We also
compared these naturally occurring patterns with the histone
modifications of murine ES cells, detecting large differences in
the methylation patterns of histone H3 lysines 27 and 36 between
pluripotent ES cells and pluripotent cells from Xenopus blastulae.
By combining all detected modification transitions we could cluster
their patterns according to their embryonic origin, defining
specific histone modification profiles (HMPs) for each
developmental stage. To our knowledge, this data set represents the
first compendium of covalent histone modifications and their
quantitative flux during normogenesis in a vertebrate model
organism. The HMPs indicate a stepwise maturation of the embryonic
epigenome, which may be causal to the progressing restriction of
cellular potency during development.