Hi, I would also refer to the papers of Albin Sandelin (see http://albinsandelin.wixsite.com/sandelinlab/publications) . His lab found out that promoters and enhancers can both initiate transcription and act interchangeably. See review http://www.sciencedirect.com/science/article/pii/S0168952515001043

Hi Ajit and Johan, thanks for the excellent articles. I am very well aware of those. There is no ambiguity in an enhancer and a promoter behaving somewhat in a similar fashion as stand-alone transcriptional units.

My question relates to those enhancer-promoter pairs that exist in contact. Literature tells us that at in-contact enhancer-promoter pairs, either both stay inactive (model A in the attached cartoon), or both transcribe (model B). But, I have thus far not seen an example where only the enhancer (or only the promoter; but NOT both) is transcribing (model C in the cartoon). I was seeking any example of this model C that may possibly be found in literature or data-mining. My own logic tells me that this example does not exist. But wanted the opinion/expertise of others on this matter.

This question is important if we consider the transcription at in-contact enhancer and promoter as a coordinated event, which, ultimately, will warrant molecular elucidation of that coordination.

Hi Anil,

OK, I understand better your question. I think the semantic 'active' in your cartoon is misleading as I would personally call an enhancer 'active' if it is able to drive the expression of its target gene. I imagine that there may be cases where the enhancer is transcribed but not linked with its target promoter and others where the enhancer is linked to its promoter, enhancing the expression of the flanking gene but not transcribed itself. For instance, I worked on the enhancer of FLOWERING LOCUS T in Arabidopsis thaliana and we were not able to find transcripts derived from the enhancer though the target gene FLOWERING LOCUS T is strongly transcribed, so this could constitute an example for your model C (note that eRNAs are poorly investigated in plants). Hope this help.

Hi Johan,

Thank you. You are right, an 'active' enhancer is the one that is actively stimulating its target promoter transcription. Since all such enhancers--in my understanding--thus far were observed to undergo transcription themselves, I took the liberty of calling an enhancer 'active' when it itself was transcribing.

It is interesting to learn about the FT locus. Since you said that eRNAs are poorly investigated in plants, are you absolutely sure that the FT enhancer does not transcribe? Many genomic transcripts are so labile (or so few in number) that they do not show up in conventional assays, and they require inactivation/deletion/KD of the exosome complex to be properly detected. Besides, do you know that this enhancer is 'in contact' with the promoter at the time that the promoter is strongly transcribing (and the eRNA detection attempts were made at the same/shortly preceding time)? Also, are you sure that this enhancer only, and not any other regulatory element, is impacting FT promoter transcription?

I am trying to understand if there is a mutualism between enhancer and promoter transcription, and if there is, then what is the molecular basis of that mutualism. The FT locus, as you describe, would be an exception to this notion, and I would need to learn about this locus. Please advise me if your work has been published, or of any relevant literature.

Thanks again,

Anil

Hi Anil,

Indeed, there may be eRNAs at the enhancer of FT that we overlooked so I cannot guarantee their absence. Several non-coding RNAs, smRNAs, and mRNA datasets did not reveal them though. About the contact of the enhancer with the promoter at the FT locus, there are two papers published (including one from my previous group): Cao et al., 2014 (doi/10.1105/tpc.113.120352) and Liu et al., 2014 (DOI: 10.1038/ncomms5558). In these papers, interactions within the FT locus were investigated using 3C (chromosome conformation capture). Unfortunately, the interactions between the promoter of FT and its upstream region are discordant between the 2 studies. Several factors can explain this discrepancy, including the fact that relatively short distances were probed (less than 5 kb). At the end, I would be really carefull when interpreting 3C data since this method is really tricky (see Jamge et al., 2017, doi.org/10.1186/s13007-017-0251-x).

About other enhancers at FT locus, yes, there are others, but you will have to wait a bit more for our next paper to get out ;)

What do you mean by mutualism exactly?

To get more information about enhancers in plants, I refer you to our review (Weber et al., 2016, doi: 10.1016/j.tplants.2016.07.013).

Best regards,

Johan