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One can classify the effects of Transcription Factors (TF) on gene expression into two types: it either enhance or repress the gene expression.

I have always been told that most of transcription factors functions act to enhance gene expression rather than repress gene expression. Assuming this is true, my question is why are activators more common than repressors?. Is there for example a mechanistic explanation for that (cost less energy to enhance or the enhancement pathway is easier to evolve)?

From wikipedia

While activators can interact directly or indirectly with the core machinery of transcription through enhancer binding, repressors predominantly recruit co-repressor complexes leading to transcriptional repression by chromatin condensation of enhancer regions.

The mechanisms are different and it sounds a likely cause of the overrepresentation of enhancement function of transcription factors in genomes but it is not obvious to me why activators and repressors have to have use different mechanisms and it is not obvious to me either why these different mechanisms would yield to a ratio of repressors to activators other than $\frac{1}{2}$.

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    $\begingroup$ Do you have a reference for this claim? Also, keep in mind that simply the absence of an activator can be repressive. In other words, one mechanism of repressing gene expression is to not express the activator. $\endgroup$
    – canadianer
    Dec 12, 2014 at 22:54
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    $\begingroup$ They do not fall into clear groups. A transcription factor can activate one gene and repress another. Either by binding to its regulatory region or by upregulating another suppressor (which would be a secondary effect). $\endgroup$
    – Chris ♦
    Dec 12, 2014 at 23:01
  • $\begingroup$ No I don't unfortunately. But as I have heard that several times I kinda felt that this was common knowledge. "absence of an activator can be repressive". That sounds weird to me. Isn't just a matter of relativity? The point is that still, activators are more common than repressors (assuming this is true) and so why? is it easier to evolve activator than suppressor? $\endgroup$
    – Remi.b
    Dec 12, 2014 at 23:02
  • $\begingroup$ @Chris Oh good point! But still most functions are repressive (assuming this is true) so the question still hold. If it is not common knowledge that activators are more common than repressors I may have better to first ask a question about that to make sure my assumption is correct. $\endgroup$
    – Remi.b
    Dec 12, 2014 at 23:03
  • $\begingroup$ Hypothesizing I would say this is because of different control pathways. You can turn on genes on a pretty sensitive way (fine regulated and only a few at a time with a lot of regulators). You can then use different circuits to regulate the downregulation. $\endgroup$
    – Chris ♦
    Dec 12, 2014 at 23:06

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I can answer this question only based on guesses because I am not really sure about your claim that activators are higher in number than repressors. So consider this as an extended comment.

While activators can interact directly or indirectly with the core machinery of transcription through enhancer binding, repressors predominantly recruit co-repressor complexes leading to transcriptional repression by chromatin condensation of enhancer regions

Not really true. A repressor can simply sit on the the promoter and prevent RNAP from binding the to the latter.

Abstract

Transcriptional repressors are usually viewed as proteins that bind to promoters in a way that impedes subsequent binding of RNA polymerase. Although this repression mechanism is found at several promoters, there is a growing list of repressors that inhibit transcription initiation in other ways. For example, several repressors allow the simultaneous binding of RNA polymerase to the promoter, but interfere with subsequent events of the initiation process, eventually inhibiting transcription initiation. The recent increase in the number of repressors for which the repression mechanism has been characterized in detail has shown an amazing variety of strategies to repress transcription initiation. It is not surprising to find that the repression mechanism used is usually exquisitely adapted to the characteristics of the promoter and of the repressor involved.

Some justification on why the number activators would be more:

A network perspective:

Lets assume an that gene-A somehow causes the repression of the gene-B. This repression can be either direct (A being a repressor of B) or indirect via some other genes. In the case of indirect regulation you just need one repressor in the network path A → B to result in repression of the latter.

So all repressive paths would minimally require only one repressor, all other steps in the path can be activation; whereas in an activating path you would need 'n' activators for 'n' steps.

Post-transcriptional Regulation:

Now if you include post-transcriptional regulation then you can find more number of repressors: miRNAs (2588 reported in humans: miRbase-21) and many proteins as well (For an e.g. see here). Most cases of events leading to translational activation are actually derepression. It is logical in a way because an mRNA is a temporary product; it should not by default require an additional signal to start producing proteins.

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  • $\begingroup$ Thanks. I appreciate these speculations based on my non-referenced statement. Your explanations make quite intuitive sense. $\endgroup$
    – Remi.b
    Jan 12, 2015 at 14:11

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