title: Drosophila Cyclin G and epigenetic maintenance of gene expression during development.
abstract: BACKGROUND
  Cyclins and cyclin-dependent kinases (CDKs) are essential for cell cycle regulation and are functionally associated with proteins involved in epigenetic maintenance of transcriptional patterns in various developmental or cellular contexts. Epigenetic maintenance of transcription patterns, notably of Hox genes, requires the conserved Polycomb-group (PcG), Trithorax-group (TrxG), and Enhancer of Trithorax and Polycomb (ETP) proteins, particularly well studied in Drosophila. These proteins form large multimeric complexes that bind chromatin and appose or recognize histone post-translational modifications. PcG genes act as repressors, counteracted by trxG genes that maintain gene activation, while ETPs interact with both, behaving alternatively as repressors or activators. Drosophila Cyclin G negatively regulates cell growth and cell cycle progression, binds and co-localizes with the ETP Corto on chromatin, and participates with Corto in Abdominal-B Hox gene regulation. Here, we address further implications of Cyclin G in epigenetic maintenance of gene expression.
  
  
  RESULTS
  We show that Cyclin G physically interacts and extensively co-localizes on chromatin with the conserved ETP Additional sex combs (ASX), belonging to the repressive PR-DUB complex that participates in H2A deubiquitination and Hox gene silencing. Furthermore, Cyclin G mainly co-localizes with RNA polymerase II phosphorylated on serine 2 that is specific to productive transcription. CycG interacts with Asx, PcG, and trxG genes in Hox gene maintenance, and behaves as a PcG gene. These interactions correlate with modified ectopic Hox protein domains in imaginal discs, consistent with a role for Cyclin G in PcG-mediated Hox gene repression.
  
  
  CONCLUSIONS
  We show here that Drosophila CycG is a Polycomb-group gene enhancer, acting in epigenetic maintenance of the Hox genes Sex combs reduced (Scr) and Ultrabithorax (Ubx). However, our data suggest that Cyclin G acts alternatively as a transcriptional activator or repressor depending on the developmental stage, the tissue or the target gene. Interestingly, since Cyclin G interacts with several CDKs, Cyclin G binding to the ETPs ASX or Corto suggests that their activity could depend on Cyclin G-mediated phosphorylation. We discuss whether Cyclin G fine-tunes transcription by controlling H2A ubiquitination and transcriptional elongation via interaction with the ASX subunit of PR-DUB.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UMR 7622, Developmental Biology, 9, quai Saint-Bernard, F-75005 Paris, France ; CNRS, IBPS, UMR 7622, Developmental Biology, 9, quai Saint-Bernard, F-75005 Paris, France.
authors.forename: Camille A
authors.initials: CA
authors.lastname: Dupont
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UMR 7622, Developmental Biology, 9, quai Saint-Bernard, F-75005 Paris, France ; CNRS, IBPS, UMR 7622, Developmental Biology, 9, quai Saint-Bernard, F-75005 Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Dardalhon-Cuménal
authors.affiliation: Lillehei Heart Institute and Department of Pediatrics, University of Minnesota, 2231 6th Street SE, Minneapolis, MN 55455 USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kyba
authors.affiliation: Department of Zoology, University of British Columbia, 6270 University Boulevard, V6T 1Z4 Vancouver, BC Canada.
authors.forename: Hugh W
authors.initials: HW
authors.lastname: Brock
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UMR 7622, Developmental Biology, 9, quai Saint-Bernard, F-75005 Paris, France ; CNRS, IBPS, UMR 7622, Developmental Biology, 9, quai Saint-Bernard, F-75005 Paris, France.
authors.forename: Neel B
authors.initials: NB
authors.lastname: Randsholt
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UMR 7622, Developmental Biology, 9, quai Saint-Bernard, F-75005 Paris, France ; CNRS, IBPS, UMR 7622, Developmental Biology, 9, quai Saint-Bernard, F-75005 Paris, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Peronnet
keywords: Cyclin G; Homeotic; Polycomb; Trithorax