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I have noticed that some TF binding sites are located in the introns of the genes.

I am puzzled about whether the TF only binds to DNA in the initiation stage of transcription and will detach during transcription. (I am thinking if the TF bind to the sense strand, it will block the PoLII for transcription, thus they should be removed.)

Many thanks in advance.

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2 Answers 2

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As Armatus said TF can remain bound without an effect.

There are some alternative explanations:

  1. Promoters need not be always upstream to the Transcription Start Site (TSS). There are promoters called Downstream Promoter Elements that are actually downstream to TSS.
  2. There can be alternate TSS within the introns
  3. TF bound to intron may regulate elongation or splicing rather than initiation. [Elongation can also be regulated especially when a gene is poised for expression. RNApolymerase stalling is a well known phenomenon and is affected by epigenetic marks. Since splicing happens co-transcriptionally there can be DNA marks that affect the process. Although it has not been shown whether such a thing happens, but Intron-Exon boundaries are known to have a distinct nucleosomal pattern.{1, 2, 3}]
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Hi, Thanks for pointing out the papers. I will read them carefully –  tky Jun 12 '13 at 12:11

Even in a quiescent state, DNA is bound to a lot of proteins. It is not a lone double-helix of DNA with an occasional protein attaching here or there. Rather, it is tightly wrapped around histones, which themselves have other proteins attaching and detaching constantly. Repair enzymes are always whizzing about and fixing the random damage that occurs in DNA naturally, and transcription factors may be sitting on the DNA for a while and then diffusing away again without doing anything. There are probably more proteins around that I've forgotten.

As you can see, the nucleus, DNA and in general the cell interior are extremely crowded spaces, and for transcription to happen it takes more than just removing some TFs attached to intronic sequences. Histones need to be modified to repel each other and make space. Ultimately, all proteins will need to detach for a short time when RNA polymerase comes through. If they don't, polymerase will stall until they move away, or it may simply fall off, producing an incomplete RNA fragment which will be degraded quickly. Another polymerase will come along soon enough and produce a new transcript if the promotor is still in a permissive state.

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Hi,Armatus,Thanks for the detailed explanation! I didn't know nucleus is such a crowed place. I am wondering if the detach process of TF from DNA can be visualized under single molecular microscope. –  tky Jun 12 '13 at 12:16
    
Microscopy at such resolutions is possible using atomic force microscopy and transmission electron microscopy, but both of these are extremely complex procedures and require the sample to be fixed - i.e. dead. –  Armatus Jun 12 '13 at 12:19
    
I see, so it is not possible to observe in vivo. Thanks again~ –  tky Jun 12 '13 at 15:45

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