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Cell Rep. 2014 Oct 9;9(1):219-33. doi: 10.1016/j.celrep.2014.08.072. Epub 2014 Oct 2.

Cooperativity, specificity, and evolutionary stability of Polycomb targeting in Drosophila.

Author information

1
Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France.
2
Department of Computer Science and Applied Mathematics and Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 7610001, Israel.
3
Montpellier GenomiX IBiSA, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France.
4
Department of Computer Science and Applied Mathematics and Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: amos.tanay@weizmann.ac.il.
5
Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France. Electronic address: giacomo.cavalli@igh.cnrs.fr.

Abstract

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.

PMID:
25284790
DOI:
10.1016/j.celrep.2014.08.072
[Indexed for MEDLINE]
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