Academic journal article Genetics

Functional Characterization of the dRYBP Gene in Drosophila

Academic journal article Genetics

Functional Characterization of the dRYBP Gene in Drosophila

Article excerpt

ABSTRACT

The Drosophila dRYBP gene has been described to function as a Polycomb-dependent transcriptional repressor. To determine the in vivo function of the dRYBP gene, we have generated mutations and analyzed the associated phenotypes. Homozygous null mutants die progressively throughout development and present phenotypes variable both in their penetrance and in their expressivity, including disrupted oogenesis, a disorganized pattern of the syncytial nuclear divisions, defects in pattern formation, and decreased wing size. Although dRYBP mutations do not show the homeotic-like phenotypes typical of mutations in the PcG and trxG genes, they enhance the phenotypes of mutations of either the Sex comb extra gene (PcG) or the trithorax gene (trxG). Finally, the dRYBP protein interacts physically with the Sex comb extra and the Pleiohomeotic proteins, and the homeotic-like phenotypes produced by the high levels of the dRYBP protein are mediated through its C-terminal domain. Our results indicate that the dRYBP gene functions in the control of cell identity together with the PcG/trxG proteins. Furthermore, they also indicate that dRYBP participates in the control of cell proliferation and cell differentiation and we propose that its functional requirement may well depend on the robustness of the animal.

PATTERN formation during animal development requires the controlled spatial and temporal regulation of gene expression. Once gene transcriptional states have been established, their maintenance during cellular proliferation is crucial for the normal development of the organism. The Polycomb (PcG) and the trithorax (trxG) groups of genes play a pivotal role in this process (for a recent review see Schuettengruber et al. 2007). The PcG genes are required for the maintenance of the repressed state while the trxG are needed for the maintenance of the active state. The PcG and trxG genes were first identified in the fly Drosophila melanogaster, due to their role in morphogenesis as regulators of homeotic gene expression (Lewis 1978; Ju?rgens 1985; Breen and Harte 1991; for a review see Ringrose and Paro 2004). However, it is now clear that the PcG and trxG genes also have relevant roles in other biological processes, such as hematopoiesis, stem cell renewal, control of cell proliferation, and tumorigenesis (van der Lugt et al. 1994; Valk-Lingbeek et al. 2004; Brock and Fisher 2005; Ferres-Marco et al. 2006; Martinez and Cavalli 2006; Sparmann and Van Lohuizen 2006).

Central to PcG/trxG epigenetic-mediated mechanisms is the recruitment and formation of multimeric protein complexes. In Drosophila, three major protein complexes containing PcG proteins have been isolated. The first identified were the complexes Polycomb repressive complex 1 (PRC1) (Shao et al. 1999) and PRC2 (Cao et al. 2002; Czermin et al. 2002; Kuzmichev et al. 2002; Muller et al. 2002). The core of PRC1 includes Polycomb (PC), Posterior sex combs (PSC), the E3 ubiquitin ligase Sex comb extra (SCE), and Polyhomeotic (PH). The core of PRC2 is composed of the histone methyl transferase Enhancer of zeste [E(Z)], Suppressor of zeste 12 [SU(Z)12], Extra sex combs (ESC), and Nurf-55. The third repressive complex, pleiohomeotic repressor complex (PHORC), containing the pleiohomeotic (PHO) protein, has recently been isolated fromDrosophila embryos (Klymenko et al. 2006). Three trxG complexes have been identified: trithorax acetylation complex (TAC), NURF, and the SWI/SNF (for reviews see Grimaud et al. 2006b; Schwartz and Pirrotta 2007). There are other PcG/ trxG proteins that do not form part of the core of these complexes, but still are associated with them and, therefore, have been classified as PcG/trxG-associated proteins (Otte and Kwaks 2003).

While much is known about the roles of the PcG/trxG proteins in the Drosophila morphogenesis, less is known about their role in biological processes such as the control of cellular proliferation and differentiation during development. …

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