Certain transposons appear to be subject to a
mode of regulation known as over-expression inhibition. This was first observed
with the eukaryotic transposons Tc1/mariner
Lampe (Lampe et al., 1998)(Lohe & Hartl,
1996, Hartl et al., 1997) where increasing the concentration of transposase results in a reduction in the
level of transposition. It was subsequently observed with the sleeping beauty
transposon (Geurts et al., 2003) (Zayed, et al., 2004). It also occurs in vivo in mice (Karsi, et al., 2001)(Mikkelsen, et
rational for this is that "infection" of a naïve cell by the transposon results
in a burst of transposition which is then attenuated by overproduction
inhibition. This is then followed by gradual decay of the transposon.
The Chalmers lab (Claeys Bouuaert,
et al., 2013) has provided an interesting and compelling explanation
of this effect. Using the mariner family transposon Hsmar1 they present convincing data implying that overproduction inhibition
occurs during transpososome assembly and is due to a combination of the
multimeric state of the transposase coupled with competition for transposase binding
sites at the Hsmar1 ends (Bouuaert, et al.,
2014, Tellier, et al., 2015).
The model (assembly-site-occlusion model) is based on the presence of
transposase multimers (dimers) to the exclusion of monomers, in other words,
end-binding required a dimeric transposase. At low transposase/transposon
ratios, one dimer can bind both transposon ends resulting in the ordered
assembly of the transpososome. An increase in the transposase dimer/transposon
ratio results in binding of dimers to both transposon ends, preventing
transpososome assembly. The model not only explains the in vivo transposase dose-response for Hsmar1 but also for the related Sleeping
Beauty (SB) and piggyBac (PB) transposons. As yet, no
information is at present available concerning the relevance of this mode of
regulation to prokaryotic transposable elements.
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