Hi Chongzhi,

The essential difference between ChIA-PET and HiC is that ChIA-PET includes an Immuno-precipitation step (using an anti-body) to enrich for chromatin that is bound by a specific protein.

Therefore, in a ChIA-PET experiment the chromatin interactions can only be determined for those parts of the genome that have a binding-site for the protein of interest (or another kind of interaction with the protein). In this way, interaction networks can for instance be determined for transcription factors, insulator proteins (CTCF) or for the transcription machinery (RNA-PolII, revealing which genes may potentially cluster at transcription factories).

In a HiC experiment all chromatin interactions within the entire genome can be determined. The bioin-antibody has a different function, which is to enrich for chromatin fragments that represent genuine chromatin interactions, as the biotin-group should have only been added to those genomic sites that were later ligated together.

Overall, a ChIA-PET experiment therefore gives information about the (potential) role of proteins in structuring 3D genome organization. A HiC data set describes 3D genome organization at a truely genome-wide scale, but to understand which agents may have a role in structuring this organization, we need to correlate the data to external datasets (e.g. ChIP-seq).

Clear!  Thank you so much

Daan Noordermeer's answer is very accurate.

There was a review published earlier this year in Nature Methods which explains and compares all the current chromosome conformation capture methods. I found it very informative. Here is the PubMed link : https://www.ncbi.nlm.nih.gov/pubmed/28139673

Daan Noordermeer Thanks for your great answer. I would like to know how do you find the protein of interest?