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HIPPIE2: a method for fine-scale identification of physically interacting chromatin regions.

TitleHIPPIE2: a method for fine-scale identification of physically interacting chromatin regions.
Publication TypeJournal Article
Year of Publication2020
AuthorsKuksa PP, Amlie-Wolf A, Hwang Y-C, Valladares O, Gregory BD, San Wang L-
JournalNAR Genom Bioinform
Date Published2020 Jun

Most regulatory chromatin interactions are mediated by various transcription factors (TFs) and involve physically interacting elements such as enhancers, insulators or promoters. To map these elements and interactions at a fine scale, we developed HIPPIE2 that analyzes raw reads from high-throughput chromosome conformation (Hi-C) experiments to identify precise loci of DNA physically interacting regions (PIRs). Unlike standard genome binning approaches (e.g. 10-kb to 1-Mb bins), HIPPIE2 dynamically infers the physical locations of PIRs using the distribution of restriction sites to increase analysis precision and resolution. We applied HIPPIE2 to Hi-C datasets across six human cell lines (GM12878, IMR90, K562, HMEC, HUVEC, NHEK) with matched ENCODE/Roadmap functional genomic data. HIPPIE2 detected 1042 738 distinct PIRs, with high resolution (average PIR length of 1006 bp) and high reproducibility (92.3% in GM12878). PIRs are enriched for epigenetic marks (H3K27ac, H3K4me1) and open chromatin, suggesting active regulatory roles. HIPPIE2 identified 2.8 million significant PIR-PIR interactions, 27.2% of which were enriched for TF binding sites. 50 608 interactions were enhancer-promoter interactions and were enriched for 33 TFs, including known DNA looping/long-range mediators. These findings demonstrate that the novel dynamic approach of HIPPIE2 ( enables the characterization of chromatin and regulatory interactions with high resolution and reproducibility.

Pubmed Link
Alternate JournalNAR Genom Bioinform
PubMed ID32270138
PubMed Central IDPMC7106622
Grant ListR01 GM099962 / GM / NIGMS NIH HHS / United States
T32 AG000255 / AG / NIA NIH HHS / United States

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