An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment

Magnus D Lynch, Andrew J H Smith, Marco De Gobbi, Maria Flenley, Jim R Hughes, Douglas Vernimmen, Helena Ayyub, Jacqueline A Sharpe, Jacqueline A Sloane-Stanley, Linda Sutherland, Stephen Meek, Tom Burdon (+3 others)
2011 EMBO Journal  
The role of DNA sequence in determining chromatin state is incompletely understood. We have previously demonstrated that large chromosomal segments from human cells recapitulate their native chromatin state in mouse cells, but the relative contribution of local sequences versus their genomic context remains unknown. In this study, we compare orthologous chromosomal regions for which the human locus establishes prominent sites of Polycomb complex recruitment in pluripotent stem cells, whereas
more » ... corresponding mouse locus does not. Using recombinationmediated cassette exchange at the mouse locus, we establish the primacy of local sequences in the encoding of chromatin state. We show that the signal for chromatin bivalency is redundantly encoded across a bivalent domain and that this reflects competition between Polycomb complex recruitment and transcriptional activation. Furthermore, our results suggest that a high density of unmethylated CpG dinucleotides is sufficient for vertebrate Polycomb recruitment. This model is supported by analysis of DNA methyltransferase-deficient embryonic stem cells. The EMBO Journal VOL 31 | NO 2 | 2012 EMBO THE EMBO JOURNAL THE EMBO JOURNAL
doi:10.1038/emboj.2011.399 pmid:22056776 pmcid:PMC3261560 fatcat:f7yffl6lyzfe5ps6cppxobsllq