Principles of nucleation of H3K27 methylation during embryonic development
- Simon J. van Heeringen,
- Robert C. Akkers,
- Ila van Kruijsbergen,
- M. Asif Arif,
- Lars L.P. Hanssen,
- Nilofar Sharifi and
- Gert Jan C. Veenstra1
- ↵* Corresponding author; email: g.veenstra{at}ncmls.ru.nl
Abstract
During embryonic development, maintenance of cell identity and lineage commitment requires the Polycomb-group PRC2 complex, which catalyzes histone H3 lysine 27 trimethylation (H3K27me3). However, the developmental origins of this regulation are unknown. Here we show that H3K27me3 enrichment increases from blastula stages onward in embryos of the Western clawed frog (Xenopus tropicalis) within constrained domains strictly defined by sequence. Strikingly, although PRC2 also binds widely to active enhancers, H3K27me3 is only deposited at a small subset of these sites. Using a Support Vector Machine algorithm these sequences can be predicted accurately on basis of DNA sequence alone, with a sequence signature conserved between humans, frog and fish. These regions correspond to the subset of blastula-stage DNA methylation-free domains that are depleted for activating promoter motifs and enriched for motifs of developmental factors. These results imply a genetic-default model in which a pre-existing absence of DNA methylation is the major determinant of H3K27 methylation when not opposed by transcriptional activation. The sequence and motif signatures reveal the hierarchical and genetically inheritable features of epigenetic cross-talk which impose constraints on Polycomb regulation and guide H3K27 methylation during exit of pluripotency.
- Received April 26, 2013.
- Accepted November 27, 2013.
- Published by Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
