Thanks again for your suggestion! I found the article to be very clear with a clever experiment design and kinetic modeling.

My second query is about the transcriptional insulation imposed by the CTCF boundaries. The authors seem to suggest that the CTCF boundaries do not alter the enhancer-promoter contact probabilities but insulate transcription by other mechanisms. What other active mechanisms could account for this?

Do we have any experiments that measure contact frequencies between promoters and enhancers?

I had a few queries after reading the article. One of the core components of the model proposed in the article is that the enhancer-promoter interaction timescales are a few seconds or less. These were also the fastest dynamics in comparison to the rest of the processes.

This is all quite exciting! Thanks for sharing. I'm now reading the articles you recommended and will be happy to update my understanding once I am through these articles. I especially love the experiment performed in the first article you recommended Zuin et. al. 2022. Such a clean experiment!!

This is exactly the kind of information I was looking for. Thanks a ton!

Pre-Initiation Complex: RNA Pol II + GTFs

Enhancer: Distal regulatory elements that bind TFs and TCoFs to enhance the transcription at core promoters.

What about the distance in 3D space as opposed to the sequence distance? Do topologies of DNA that bring an enhanced from a completely different chromosome together with a core promoter enhance its transcription?

I have so many questions here. What’s the difference between GTFs and TFs that bind at enhancers? Is the distance between the enhancer and core promoter completely irrelevant?

What’s cool is that these enhancers increase the transcription irrespective of its distance and orientation from the core promoter.

Distal regulatory sequences called Enhancers can bind proteins called transcription factors (TFs) and recruit transcription cofactors (TCoFs) that can enhance the transcription from a core promoter.

Core promoter: TSS + ~50 bp flanking it. Binds RNA Pol II and GTFs. Low basal activity.

Additionally the basal activity of transcription from a core promoter is low. I wonder if this is sequence dependent and if one can predict the basal expression rate just from the core promoter sequence.

I wonder what these GTFs are and if they bind to the RNA Pol II or the core promoter.