biomolbioandco

Science, discussed.

A Time for Transcription (Factors)

I’ve been postponing this post for a while, hoping to find the time to expand the analysis, but time seems to elude me at present, so I’ve decided to condense my thoughts and get it out anyway.

In the last few months, my inbox, twitter feed and Chrome tabs have been filling up with papers that focus on transcription factors.

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This shouldn’t surprise me, as this is a topic I’m interested in and for which I have some paper alerts. However, there seem to be more more papers than usual, including a growing number of preprint submissions. Some I have covered before on this blog, here and here:

Evolution of Conditional Cooperativity Between HOXA11 
and FOXO1 Though Allosteric Regulation
http://dx.doi.org/10.1101/014381
Exonic Transcription Factor Binding Directs Codon 
Choice and Affects Protein Evolution
http://dx.doi.org/10.1126/science.1243490
Reassessing the “Duon” Hypothesis of Protein Evolution
http://dx.doi.org/10.1093/molbev/msu409

The first paper covers the molecular basis of how (some) transcription factors seem to be working, while the latest two discuss (different) views on the possible moonlighting functions of transcription factors, namely the possibility that spurious binding sites might constrain the evolution of coding regions (hence genetic elements TFs do not have any direct interaction with). Another recent preprints tries to understand a different aspect of TFs evolution: the role triplet expansions might have played.

Key role of amino acid repeat expansions in the functional 
diversification of duplicated transcription factors
bioRxiv
http://dx.doi.org/10.1101/014910

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The attention to role gene expansion plays in protein evolution is gaining momentum, and rightly so: it could very well be a major driving force in functional evolution, in particular in higher eukaryotes where the fidelity of DNA amplification is considerably higher (and hence penalises the occurrence of single point mutations).

However, yet another preprint suggests functional evolution follows a much more complex pathway in which the environment (or more precisely the existence of a fixed selective pressure) works as an evolutionary trap to functional innovation:

Breaking through evolutionary constraint by environmental 
fluctuations 
bioRxiv
http://dx.doi.org/10.1101/016790

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I however find very interesting that a number of recent studies on TFs now focus on the engineering of altered TFs for bespoke applications. As an example, see:

Engineering Transcriptional Regulator Effector Specificity 
using Computational Design and In Vitro Rapid Prototyping: 
Developing a Vanillin Sensor
bioRxiv
http://dx.doi.org/10.1101/015438

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Although this shouldn’t surprise in the light of Synthetic Biology, it seems to me as a sort of informed return to the origins: isn’t the yeast two hybrid system the best example of re-engineered transcription factors?

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About Pietro Gatti

Interested in discussing (good) Science Lover of coffee & good films. Ideas all & only my own.

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