Cyclin G: A potential mitotic bookmark and its role in developmental stability through transcriptional regulation
Résumé
In Drosophila melanogaster, the atypical cyclin, Cyclin G (CycG), is a transcriptional regulator that maintains cell growth homeostasis and developmental stability. The expression of a potentially more stable form of CycG, CycGΔPEST, has been shown to inhibit the G1/S transition of the cell cycle, slow development 1 , and lead to a loss of correlation between cell size and total cell number in wings of flies2 . Furthermore, flies expressing CycGΔPEST have a high fluctuating asymmetry, notably of wings, indicating a high developmental noise2 . CycG also interacts genetically and physically with several subunits of the Polycomb PRC1 and PR-DUB transcriptional repressor complexes, which regulates developmental processes3 . Mutants for these complexes exhibit increased CycG-induced fluctuating asymmetry in wings, with extreme effects in mutants for the ubiquitinase Sce of PRC1 and the deubiquitinase Calypso of PR-DUB. CycG physically interacts with both enzymes and can be ubiquitinated, suggesting that it might be ubiquitinated/deubiquitinated by PRC1 and PR-DUB, respectively. The regulation of CycG by ubiquitination might be crucial for developmental stability. Furthermore, RNA-seq experiments on wing imaginal discs expressing CycGΔPEST show that the expression of genes involved in metabolism and mitochondrial activity decreases whereas expression of genes involved in translation increases3 . ChIP-seq experiments also reveal that CycG is enriched on the promoters of some of these genes. Strikingly, these promoters are bound by PRC1 in the same tissue. Interestingly, studies on HeLa cells suggest that promoters of homologous genes are bookmarked during mitosis by PRC1 ubiquitination of an unknown protein4 . It is hypothesized that this ubiquitinated protein could be CycG that would serve as a mitotic bookmark on its transcriptional targets.
Domaines
Sciences du Vivant [q-bio]
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