Cyclin G and the Polycomb Repressive complexes PRC1 and PR-DUB cooperate for developmental stability

PLoS Genet. 2018 Jul 11;14(7):e1007498. doi: 10.1371/journal.pgen.1007498. eCollection 2018 Jul.

Abstract

In Drosophila, ubiquitous expression of a short Cyclin G isoform generates extreme developmental noise estimated by fluctuating asymmetry (FA), providing a model to tackle developmental stability. This transcriptional cyclin interacts with chromatin regulators of the Enhancer of Trithorax and Polycomb (ETP) and Polycomb families. This led us to investigate the importance of these interactions in developmental stability. Deregulation of Cyclin G highlights an organ intrinsic control of developmental noise, linked to the ETP-interacting domain, and enhanced by mutations in genes encoding members of the Polycomb Repressive complexes PRC1 and PR-DUB. Deep-sequencing of wing imaginal discs deregulating CycG reveals that high developmental noise correlates with up-regulation of genes involved in translation and down-regulation of genes involved in energy production. Most Cyclin G direct transcriptional targets are also direct targets of PRC1 and RNAPolII in the developing wing. Altogether, our results suggest that Cyclin G, PRC1 and PR-DUB cooperate for developmental stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Chromatin / metabolism
  • Cyclin G / genetics
  • Cyclin G / metabolism*
  • Down-Regulation
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / physiology*
  • Female
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks / physiology
  • Male
  • Polycomb Repressive Complex 1 / genetics
  • Polycomb Repressive Complex 1 / metabolism*
  • Protein Binding / genetics
  • Up-Regulation
  • Wings, Animal / embryology

Substances

  • Chromatin
  • Cyclin G
  • Drosophila Proteins
  • Polycomb Repressive Complex 1

Grants and funding

This work was supported by grants of the Centre National de la Recherche Scientifique (CNRS) http://www.cnrs.fr/index.html, Sorbonne Université (SU) http://www.sorbonne-universite.fr/en, Sorbonne Universités http://www.sorbonne-universites.fr (grant SU-14-R-CDV-05-1), Fondation ARC pour la Recherche sur le Cancer https://www.fondation-arc.org (grant PJA20131200314) to FP, Fondation pour la Recherche médicale https://www.frm.org (grant FDT20160435164) to JD, Agence Nationale de la Recherche, France Génomique national infrastructure https://www.france-genomique.org/spip/spip.php?article82&lang=fr (grant ANR-10-INBS-09) to SLC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.