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Chip-Seq Of Conventional Tfs: What Are The Peaks W/O The Motif?

Hello all,

I've read several papers estimating the quality of ChIP-seq and most estimate percentage of peaks that include the consensus sequence at about 50%. Having lower FDR does not improve this very dramatically (to 70% maybe).

So what are the high confidence peaks that do not contain the target motif? What causes them? Is there a systematic study of any sort?

I'd be grateful for any pointers.

cheers

chip-seq motif
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written by predeus predeus

2 answers

Some possible explanations could be:

  1. Secondary binding/protein complexes: Another protein is binding the DNA and your ChIP:ed protein is binding to that protein.
  2. Generally open chromatin: an active regulatory region (perhaps "unlocked" by a "pioneering TF") is easier to bind to in the absence of a motif.
  3. Degenerate motif: there is actually a binding motif but it is relatively dissimilar from the consensus
  4. Artefactual regions, see e g the "black list" here: https://sites.google.com/site/anshulkundaje/projects/blacklists

Since you have an FDR it seems you have a control library so the following may not apply to your case but is interesting in general: even in negative control libraries, regions like transcription start sites give robust peaks: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005241

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written by Mikael Huss Mikael Huss

Great. Thank you for the answer and the reference.

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written by predeus predeus

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