On 2014 May 23, Leonid Teytelman commented:

Indeed, using MNase may be the solution. Please see Kasinathan S, 2014 "High-resolution mapping of transcription factor binding sites on native chromatin".

On 2014 May 22, L. Norton commented:

Nice work. Background is certainly an issue in ChIP-Seq studies and I think one way to deal with this is to examine gene expression of the proposed targets following knock-down of the transcription factor. Although this is not a perfect solution, after doing these experiments it becomes apparent that very few ChIP-Seq binding events are 'functionally significant' in a way that we expect (i.e. effect transcription). As a side note, I wonder if you or anyone else has examined the impact of sonication vs. MNase digestion on this phenomenon?

On 2014 Apr 10, Leonid Teytelman commented:

Below are other publications reporting the expression-associated ChIP artifact.

Fan X, 2009 "Where Does Mediator Bind In Vivo?" (Work in S. cerevisiae questioning reports of pervasive genome-wide binding of the Mediator complex.)

Waldminghaus T, 2010 "ChIP on Chip: surprising results are often artifacts" (Work in E. coli; also see arising correspondence Schindler D, 2013.)

Park D, 2013 "Widespread Misinterpretable ChIP-seq Bias in Yeast" (Analysis very similar to ours.)

Kasinathan S, 2014 "High-resolution mapping of transcription factor binding sites on native chromatin" (Questions specificity of standard ChIP in S. cerevisiae and at HOT regions of Drosophila. This work possibly provides a solution to the artifact with a modification of the ChIP technique.)

On 2014 Apr 10, Leonid Teytelman commented:

Below are other publications reporting the expression-associated ChIP artifact.

Fan X, 2009 "Where Does Mediator Bind In Vivo?" (Work in S. cerevisiae questioning reports of pervasive genome-wide binding of the Mediator complex.)

Waldminghaus T, 2010 "ChIP on Chip: surprising results are often artifacts" (Work in E. coli; also see arising correspondence Schindler D, 2013.)

Park D, 2013 "Widespread Misinterpretable ChIP-seq Bias in Yeast" (Analysis very similar to ours.)

Kasinathan S, 2014 "High-resolution mapping of transcription factor binding sites on native chromatin" (Questions specificity of standard ChIP in S. cerevisiae and at HOT regions of Drosophila. This work possibly provides a solution to the artifact with a modification of the ChIP technique.)

On 2014 May 22, L. Norton commented:

Nice work. Background is certainly an issue in ChIP-Seq studies and I think one way to deal with this is to examine gene expression of the proposed targets following knock-down of the transcription factor. Although this is not a perfect solution, after doing these experiments it becomes apparent that very few ChIP-Seq binding events are 'functionally significant' in a way that we expect (i.e. effect transcription). As a side note, I wonder if you or anyone else has examined the impact of sonication vs. MNase digestion on this phenomenon?