Polycomb group-dependent Cyclin A repression in Drosophila.
Polycomb group (PcG) and trithorax group (trxG) proteins are well known for their role in the maintenance of silent and active expression states of homeotic genes. However, PcG proteins may also be required for the control of cellular proliferation in vertebrates. In Drosophila, PcG factors act by associating with specific DNA regions termed PcG response elements (PREs). Here, we have investigated whether Drosophila cell cycle genes are directly regulated by PcG proteins through PREs. We have isolated a PRE that regulates Cyclin A (CycA) expression. This sequence is bound by the Polycomb (PC) and Polyhomeotic (PH) proteins of the PcG, and also by GAGA factor (GAF), a trxG protein that is usually found associated with PREs. This sequence causes PcG- and trxG-dependent variegation of the mini-white reporter gene in transgenic flies. The combination of FISH with PC immunostaining in embryonic cells shows that the endogenous CycA gene colocalizes with PC at foci of high PC concentration named PcG bodies. Finally, loss of function of the Pc gene and overexpression of Pc and ph trigger up-regulation and down-regulation, respectively, of CycA expression in embryos. These results demonstrate that CycA is directly regulated by PcG proteins, linking them to cell cycle control in vivo.
Institute of Human Genetics, Centre National de la Recherche Scientifique, 34396 Montpellier Cedex 5, France.
Anne-Marie
AM
Martinez
Sophie
S
Colomb
Jérôme
J
Déjardin
Frédéric
F
Bantignies
Giacomo
G
Cavalli
D000818:Animals; D019925:Cyclin A / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D047468:Immunoprecipitation; D017404:In Situ Hybridization, Fluorescence; D009698:Nucleoproteins / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D034622:RNA Interference; D020218:Response Elements / Q000235:genetics / Q000502:physiology*
D019925:Cyclin A; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009698:Nucleoproteins; C066770:Pc protein, Drosophila; C072820:ph-d protein, Drosophila; D063150:Polycomb Repressive Complex 1