Live analysis of position-effect variegation in Drosophila reveals different modes of action for HP1a and Su(var)3-9.

Farah J Bughio, Keith A Maggert

Proceedings of the National Academy of Sciences of the United States of America 2022 Jun 21

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Position-effect variegation (PEV) results from the juxtaposition of euchromatic and heterochromatic components of eukaryotic genomes, silencing genes near the new euchromatin/heterochromatin junctions. Silencing is itself heritable through S phase, giving rise to distinctive random patterns of cell clones expressing the genes intermixed with clones in which the genes are silenced. Much of what we know about epigenetic inheritance in the soma stems from work on PEV aimed at identifying the components of the silencing machinery and its mechanism of inheritance. The roles of two central gene activities-the Su(var)3-9-encoded histone H3-lysine-9 methyltransferase and the Su(var)205-encoded methyl-H3-lysine-9 binding protein heterochromatin protein 1 (HP1a)-have been inferred from terminal phenotypes, leaving considerable gaps in understanding of how PEV behaves through development. Here, we investigate the PEV phenotypes of Su(var)3-9 and Su(var)205 mutations in live developing tissues. We discovered that mutation in Su(var)205 compromises the initial establishment of PEV in early embryogenesis. Later gains of heterochromatin-induced gene silencing are possible but are unstable and lost rapidly. In contrast, a strain with mutation in Su(var)3-9 exhibits robust silencing early in development but fails to maintain it through subsequent cell divisions. Our analyses show that, while the terminal phenotypes of these mutations may appear identical, they have arrived at them through different developmental trajectories. We discuss how our findings expand and clarify existing models for epigenetic inheritance of heterochromatin-induced gene silencing.

Citation

Farah J Bughio, Keith A Maggert. Live analysis of position-effect variegation in Drosophila reveals different modes of action for HP1a and Su(var)3-9. Proceedings of the National Academy of Sciences of the United States of America. 2022 Jun 21;119(25):e2118796119