Cooperativity, specificity, and evolutionary stability of polycomb targeting in Drosophila

Bernd Schuettengruber, Noa Oded Elkayam, Tom Sexton, Marianne Entrevan, Shani Stern, Aubin Thomas, Eitan Yaffe, Hugues Parrinello, Amos Tanay, Giacomo Cavalli

Research output: Contribution to journalArticlepeer-review


Metazoan genomes are partitioned into modular chromosomal domains containing active or repressive chromatin. In flies, Polycomb group (PcG) response elements (PREs) recruit PHO and other DNA-binding factors and act as nucleation sites for the formation of Polycomb repressive domains. The sequence specificity of PREs is not well understood. Here, we use comparative epigenomics and transgenic assays to show that Drosophila domain organization and PRE specification are evolutionarily conserved despite significant cis-element divergence within Polycomb domains, whereas cis-element evolution is strongly correlated with transcription factor binding divergence outside of Polycomb domains. Cooperative interactions of PcG complexes and their recruiting factor PHO stabilize PHO recruitment to low-specificity sequences. Consistently, PHO recruitment to sites within Polycomb domains is stabilized by PRC1. These data suggest that cooperative rather than hierarchical interactions among low-affinity sequences, DNA-binding factors, and the Polycomb machinery are giving rise to specific and strongly conserved 3D structures in Drosophila.

Original languageEnglish
Pages (from-to)219-233
Number of pages15
JournalCell Reports
Issue number1
StatePublished - 9 Oct 2014
Externally publishedYes

Bibliographical note

Funding Information:
We are grateful to Jurg Müller and Judy Kassis for providing PHO antibodies, and D. Locker for providing DSP1 antibodies. We thank Mythily Ganapathi for helpful discussions. Research at G.C.’s lab was supported by grants from the European Research Council (ERC-2008-AdG No 232947), the CNRS, the INSERM, the European Network of Excellence EpiGeneSys, the Agence Nationale de la Recherche, and the Association pour la Recherche sur le Cancer. Research at A.T.’s lab was supported by the European Research Council, the European Network of Excellence EpiGeneSys, and the Israel Science Foundation.

Publisher Copyright:
© 2014 The Authors.

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)


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