Direct - indirect binding of a transcription factor in chip-seq analysis

Question

[buffealo]

Hello,

I wonder how can I identify if the binding of a transcription factor in a chip-seq experiment to DNA is direct or indirect?

Thank you.

[Ankit]

One way is to look for a motif in peaks. If your factor interacts directly with DNA than possibly a defined motif comes out. Correlates with literature search and protein structure.

[buffealo]

For example HOMER is giving separate files for different motifs, this file contains all of the peaks but not all of them has a motif. So could it be considered as direct binding?

In example ;

(HOMER annotated motif result)

[Ankit]

Try with different tools HOMER, MEME etc. May be try +/- 10bp from summit of peak.

If same motif comes out than the probability increase for direct binding. Although this approach is just to get an idea that there is a direct interaction.

[buffealo]

Thank you. Is there a way to make the probability much higher? I mean can I do something different than those approaches?

[Ankit]

Experimental approaches can help. Bioinformatically I am not sure about more methods. Other experts can give you guidance.