Nuclear receptors can influence transcription far up- or downstream from their own binding sites by looping DNA (Rubina et al.; J Mol Bio 2004).

I am not sure how exactly the receptors first attach to the DNA (dimers on each site first or the whole complex on one site), but in any case they will need to attach to one response element, then loop the DNA and bind the other response element. It seems like something that should be obvious, but I cannot stop wondering: How do the receptors locate the other site?

Normally I would simply say: diffusion - it just randomly happens. But I imagine bending DNA in such a way would require a lot of energy; too much to just randomly waste it trying to find another site.

  • $\begingroup$ Not sure NR are actually bending a linear DNA into a loop. The loop, as Shigeta points, could already form by random coiling. Then, NR would stabilize the loop recruiting other coregulators. All together they will act like a glue. $\endgroup$ – Gianpaolo R May 9 '12 at 14:27

This probably isn't the complete answer as I don't know so much about eukaryotic transcription, but maybe I can start the answer.

First of all DNA bending can be sequence dependent - the double helix is not intrinsically straight. DNA is also pretty easy to bend - it spends most of its time coiled pretty easily around histones, and eukaryotes, supercoiled into chromatin.

In transcription though, there are proteins that come along and effect bends in the DNA or even tight loops, so that the transcription initiation complex (TIC) can be activated by transcription factors (TFs) upstream as the DNA flops over.

see this happening in this video at about :40: http://www.youtube.com/watch?v=5MfSYnItYvg&feature=related

I think in some cases there might be other proteins bound upstream of the TIC to make the influence of various TFs greater. I know in highly regulated genes (such as developmental genes in animals) transcription regulation can be impossibly complicated with lots if internal logic. The classic example is ENDO16 from sea urchin (see second image) which has scores of protein binding sites in front of it.

I was told that DNA binding proteins find their binding sites at a rate faster than diffusion. The prof told me that she thought that there might be a tendency to diffuse along the length of the DNA because of its charge. I have no reference for this, but it might help answer your question as to how the NRs pair up so quickly.

  • $\begingroup$ What a funny coincidence, I once sent that video (rather, the "advanced" one) round my course colleagues when we had biochem XD Thanks for the info and references about DNA! It's unfortunate that the most important part (your last paragraph) was only word of mouth though, because that's actually what I'm wondering :/ $\endgroup$ – Armatus May 9 '12 at 20:10

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