Like a bottle of wine, heterochromatin is no use unless you can open it. TAF250 is one protein that helps to uncork the DNA by loosening histone H1's grip on it. A paper by Pham and Sauer in Science suggests that TAF250 is more a Swiss-army knife than a corkscrew, though: it was already known to phosphorylate and acetylate histone H1, but now it adds ubiquitylation to its list of talents list.
Polyubiquitylation — adding a chain of ubiquitin molecules to proteins — is a signal for destruction, but monoubiquitylation is less well understood. Knowing that histone H1 can be monoubiquitylated, Pham and Sauer set out to discover what was doing it, and found TAF250. Ubiquitylation requires a minimum of two enzyme activities, an activator and a conjugator, which are usually on separate proteins. In vitro assays revealed that TAF250 has both. But what about in vivo ? Having identified the region of TAF250 that's necessary for histone monoubiquitylation, they created mutants that lack the activity and are heterozygous for dorsal — a maternally expressed gene important for early Drosophila development. In these mutants, expression of the dorsal -response genes twist and snail was significantly reduced, resulting in a twisted phenotype. Levels of monoubiquitylated histone were also reduced. More substrates of TAF250's ubiquitylating activity, as well as factors that ubiquitylate the other histones, may await discovery.
References
ORIGINAL RESEARCH PAPER
Pham, A.-D. & Sauer, F. Ubiquitin-activating/conjugating activity of TAF250, a mediator of activation of gene expression in Drosophila. Science 289 , 2357–2360 (2000)
FURTHER READING
Mizzen, C. A. & Allis, C. D. New insights into an old modification. Science 289, 2290–2291 (2000)
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Brooksbank, C. A molecular Swiss-army knife. Nat Rev Mol Cell Biol 1, 87 (2000). https://doi.org/10.1038/35040032
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DOI: https://doi.org/10.1038/35040032
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