RT Journal
A1 van Heeringen, Simon J.
A1 Akkers, Robert C.
A1 van Kruijsbergen, Ila
A1 Arif, M. Asif
A1 Hanssen, Lars L.P.
A1 Sharifi, Nilofar
A1 Veenstra, Gert Jan C.
T1 Principles of nucleation of H3K27 methylation during embryonic development
JF Genome Research 
JO Genome Research 
YR 2014 
FD March 01 
VO 24 
IS 3 
SP 401 
OP 410 
DO 10.1101/gr.159608.113 
UL http://genome.cshlp.org/content/24/3/401.abstract 
AB 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 the basis of DNA sequence alone, with a sequence signature conserved between humans, frogs, 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 preexisting 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 that impose constraints on Polycomb regulation and guide H3K27 methylation during the exit of pluripotency.