Question: How can I correlate ATAC-seq peak signal with enhancer ChIP-seq mark signal (H3K4me1)?
gravatar for a.rex
12 weeks ago by
a.rex170 wrote:

I have a set of ATAC-peaks which I would like to correlate, somehow, with the level of H3K4me1 flanking these peaks? This is because, H3K4me1 is a well known marker for active enhancers. Would people recommend to do a Pearson correlation between ATAC-peaks read level and H3K4me1 read level flanking the peaks? How can you go about doing this?

atac chip • 251 views
ADD COMMENTlink written 12 weeks ago by a.rex170

H3K4me1 is a well known marker for active enhancers

No, it is a histone modification associated with enhancers (or regulatory elements in general, given that the word 'enhancer' is inflationarily used in the literature for almost everything that is not a promoter and associated with either open chromatin or any of the more prominent histone modification such as H3K4me1/2 and H3K27ac), irrespective of its current stage, be it active or poised, see e.g. Ostuni 2013.

ADD REPLYlink modified 12 weeks ago • written 12 weeks ago by ATpoint13k

Yes, I realise that it can be a feature of both active and poised enhancers.

ADD REPLYlink written 12 weeks ago by a.rex170

Im not sure a correlation between read depth across ATAC and ChIP experiments is very informative, given how different the experimental techniques are (e.g. antibody based vs transposase). In general the amount of reads found in a ChIP experiment for something like a histone mark scales "linearly" with H3K4me1 density, however in ATAC-seq there is no such correlation. Maybe consider doing footprint analysis of your ATAC-seq open chromatin regions using as the input the ChIP-seq results, with something like Centipede or PIQ.

ADD REPLYlink modified 12 weeks ago • written 12 weeks ago by rbronste230

H3K4me1 is not a well known marker for active enhancers. It's for all enhancers. Assuming active enhancers have TF binding to them, the ATAC-seq signal and histone modification signal should be anti-correlated. Instead of Pearson correlation, you may need to do footprint analysis.

ADD REPLYlink written 12 weeks ago by solo777370

Hi solo7773, please allow me to remember that I already explained why the assumption that TF binding leads to decreased chromatin accessability the way you imagine it is not correct. You are mixing up decreased chromatin accessability for an entire region with the local protection of a transcription factor binding site from the transposase by protein binding. Please see my answer for the long version of this short sentence. If you do not believe me, go ahead and search for any publication using both histone modification ChIP-seq and ATAC-seq and check out the relationship there.

ADD REPLYlink written 11 weeks ago by ATpoint13k

Thanks ATpoint. Sorry for my mistake. I believe you and your answer have helped me to get better understanding. I didn't know H3K4me1 very well and I didn't think about the techniques behind H3K4me1 profiling. I should have not commented, especially when I don't know if my opinion is wrong.

ADD REPLYlink written 11 weeks ago by solo777370
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