I have found that transcriptional regulators may act as either activators or repressors, depending on their binding site position relative to the transcription start site. A binding event located upstream of the start site can enable activation, while binding over the transcription start site can cause repression. This has been seen several times for the asnC/lrp family of transcriptional regulators.

Hi Yohanes,

It is very important to check the various sequences in the promoter region where transcription factor binds (specific sequence elements to which transcription factors bind) dictates whether it acts as activator or repressor.

HSF4b acts as transcriptional activator, its spliced isoform HSF4a acts as repressor.

Please go through these articles.

1. The mammalian HSF4 gene generates both an activator and a repressor of heat shock genes by alternative splicing.

2. Developmentally dictated expression of heat shock factors: exclusive expression of HSF4 in the postnatal lens and its specific interaction with alphaB-crystallin heat shock promoter.

Hope you find some answer.

To find the transcription factor binding sites, you need to design few oligos in the promoter region and perform couple of Gel shifts and Super shifts to confirm and tamper these regions to check the function.

In bacteria, several TFs are known to have dual function. You can find references at NCBI by searching for these terms. Off the top of my head, Lrp, LexA, SoxS, MarA and CRP have all been shown to operate in both modes,

I'd like to add Helicobacter pylori NikR to the list of transcription factors which can pull double duty. However, don't search for NikR in other species and it appears that only the H. pylori homolog is both an activator and a repressor.

The mammalian tumor suppressor protein p53 is a very well studied transcriptional activator as well as a repressor. There are several reports of p53 involved in transcriptional activation and one of its well characterized target is p21. In my graduate work I have reported that p53 represses the Spindle Assembly Checkpoint (SAC) gene Cdc20( Ref: Nucleic Acids Res. 2009 May;37(8):2688-98). P53 has a consensus binding sequence comprising of two tandem recognizing sequences. These tandem sequences are separated by a 'spacer' sequence. The varying length of this spacer has been found to determine in some cases whether p53 will act as an activator or an repressor. There are several papers available discussing the dual role of p53 in transcription.

Hello All, thank you very much for your prompt response. It really opens me up beyond my knowledge. Now I know in other micro-organisms, the duality is exist. The target protein (not in E.coli and none of above)) actually has been extensively studied and all the report says it is an activator only, not repressor. So, when I got preliminary result which showing the protein also acts as a repressor, it just surprised me, because if it is true, it will be a new finding for this protein family. Now, I regain my confidence to pursue and to clarify further about this protein. I already analyzed the upstream region of the target gene for the presence of binding site, in-silico, but unfortunately the binding sequence of the protein is not conserved and difficult to predict. Maybe to prove the binding activity, other than PCR based method, the easiest would be gel-shift assay. I will look into the articles which you guys already recommended. "TF with dual function", that is the keyword that I need, thank you Ivan and thank you all.

Hello all, it seems an interesting discussion! I learned something today!

Hi Yohanes,

I am working with Rpn4 transcriptional activator of S.cerevisiae proteasome genes. It is also known as a repressor for genes encoding ubiquitin, and ubiquitin-activating enzyme. The list of my papers is on my page. When I mapped its activation domains I tryed to map its repression domain. My preliminary data show that these domains is placed close to each other but do not overlap. I also noticed that this factor is repressor when its binding site is located between TATA-box and transcription initiation site.

In Xenopus laevis you have a lot of examples (http://www.xenbase.org/): Gli3, Su(H), FoxD3, etc.

@Vladimir

"Probably, the simplest classical example of a TF that acts as a repressor or activator in different contexts can be found in the bacteriophage lambda switch system"

And it is anything but simple!

All of the comments bring up interesting and relevant points, and it's true that many TFs act as both repressors and activators. BUT in this case I think you're getting ahead of yourself. As you mentioned in your post, you can't separate direct from indirect effects at this point. Deleting almost *any* TF will cause expression of some genes to go up, and others to go down, because activators can activate repressors, and repressors can repress repressors, etc.

My point is that it's premature to be interpreting these data in terms of specific transcriptional mechanisms. This isn't that kind of experiment.

Yes Scott, I know it is premature to say or conclude anything at this point. That is why I want to know whether this duality is exist or not and I became aware now that it does exist and so there is possibility that my protein also can have dual function in terms of transcriptional regulation. Of course I will not exclude the possibility of indirect effect just like you said. Thank you for your comment.

Dear yohanes , I protein we worked on called leu3p in yeast has the duality properties you are asking for. You will your answers to Poulou et al. 2010 PLOs One. Let me know if I can be of any more help.

araC controls the arabinose operon BAD in E. coli, this way.

There are MANY examples of factors that can both activate and repress transcription (almost any factor that participates downstream of a signaling pathway, for example), and as in most concepts in biology, whenever you say that a factor is ALWAYS something, there will be an exception. So, if your experiments suggest your factor has both activator and repressor functions, go forward and test it.

In Drosophila, zygotic HUNCHBACK protein is both an activator and repressor of zygotic Kruppel. One of several cases in which positional information (ie, the position of a nucleus along a morphogen gradient) plays a role in regulating gene expression.

Lambda repressor is, perhaps the most classic example.

Ptashne M, Jeffrey A, Johnson AD, Maurer R, Meyer BJ, Pabo CO, Roberts TM, Sauer RT.

Cell. 1980 Jan;19(1):1-11.

http://www.ncbi.nlm.nih.gov/pubmed/6444544

I think FhL1 is another such example in Saccharomyces cerevisiae. FHL1 is a DNA binding protein which recruits another activator IFH1. On deletion of IFH1, the phenotype is lethal, on deletion of FHL1 the phenotype is very slow growth and on deletion of both IFH1 and FHL1 also leads to slow growth.

Another example is RAP1.

You can find loads of literature for all this.

See YY1 (human), RAP1 (yeast)

Many Rel family proteins have this functional duality.

We also studied a yeast site-specific DNA-binding protein, Hap1, that can act as both an activator and a repressor. See Mol. Cell. Biol. 27, 7414 (2007).

NF-Y.

See Mantovani R. papers from 2008.

Arp4 also. In NuA4, INO80 complexes

Does anyone know any examples that act as a repressor or an activator depending on the organism it is functioning in?

Right now I'm not working with transcription factors, but with signaling cascades. But recently I came across the paper which says that SIR2 (silent information regulator 2) which posses deacetylase activity and usually acts as transcriptional repressor, for some proteins like Foxo1 acts as transcriptional activator

Yes, of course: Lambda cI-Repressor represses a lot of genes but activates its own transcription.

Alicia, I know that LexA is typically (and exclusively as far as we know) a repressor in several organisms (e.g. E. coli) but has been reported to be both a repressor and an activator in other organisms (e.g. Rhodobacter sphaeroides; see Tapias et al. NAR 2002).