A genetic approach to the recruitment of PRC2 at the HoxD locus

Patrick Schorderet; Nicolas Lonfat; Fabrice Darbellay; Patrick Tschopp; Sandra Gitto; Natalia Soshnikova; Denis Duboule

doi:10.1371/journal.pgen.1003951

A genetic approach to the recruitment of PRC2 at the HoxD locus

PLoS Genet. 2013 Nov;9(11):e1003951. doi: 10.1371/journal.pgen.1003951. Epub 2013 Nov 7.

Authors

Patrick Schorderet¹, Nicolas Lonfat, Fabrice Darbellay, Patrick Tschopp, Sandra Gitto, Natalia Soshnikova, Denis Duboule

Affiliation

¹ National Research Center 'Frontiers in Genetics', Geneva, Switzerland ; School of Life Sciences, Federal Institute of Technology (EPFL), Lausanne, Switzerland.

Abstract

Polycomb group (PcG) proteins are essential for the repression of key factors during early development. In Drosophila, the polycomb repressive complexes (PRC) associate with defined polycomb response DNA elements (PREs). In mammals, however, the mechanisms underlying polycomb recruitment at targeted loci are poorly understood. We have used an in vivo approach to identify DNA sequences of importance for the proper recruitment of polycomb proteins at the HoxD locus. We report that various genomic re-arrangements of the gene cluster do not strongly affect PRC2 recruitment and that relatively small polycomb interacting sequences appear necessary and sufficient to confer polycomb recognition and targeting to ectopic loci. In addition, a high GC content, while not sufficient to recruit PRC2, may help its local spreading. We discuss the importance of PRC2 recruitment over Hox gene clusters in embryonic stem cells, for their subsequent coordinated transcriptional activation during development.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Base Composition
Chromatin / genetics
DNA / genetics
Drosophila Proteins / genetics*
Drosophila Proteins / metabolism
Drosophila melanogaster / genetics*
Drosophila melanogaster / growth & development
Embryonic Stem Cells / metabolism
Histone-Lysine N-Methyltransferase / genetics*
Histone-Lysine N-Methyltransferase / metabolism
Homeodomain Proteins / genetics*
Protein Binding / genetics
Response Elements / genetics*

Substances

Chromatin
Drosophila Proteins
Homeodomain Proteins
DNA
Histone-Lysine N-Methyltransferase
PRC2 protein, Drosophila

Grants and funding

This work was supported by the Ecole Polytechnique Fédérale de Lausanne (www.epfl.ch), the University of Geneva (www.unige.ch), the ERC grant SystemsHox.ch (to DD; No 232790) and the FP7 EU program IDEAL (FP-7 HEALTH.2010.2.2.2-1). PS was supported by funds from the FP7 EU program IDEAL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.