Title | HIPPIE2: a method for fine-scale identification of physically interacting chromatin regions. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Kuksa PP, Amlie-Wolf A, Hwang Y-C, Valladares O, Gregory BD, San Wang L- |
Journal | NAR Genom Bioinform |
Volume | 2 |
Issue | 2 |
Pagination | lqaa022 |
Date Published | 2020 Jun |
ISSN | 2631-9268 |
Abstract | 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 (https://bitbucket.com/wanglab-upenn/HIPPIE2) enables the characterization of chromatin and regulatory interactions with high resolution and reproducibility. |
DOI | 10.1093/nargab/lqaa022 |
Pubmed Link | https://www.ncbi.nlm.nih.gov/pubmed/32270138?dopt=Abstract |
page_expo | External |
Alternate Journal | NAR Genom Bioinform |
PubMed ID | 32270138 |
PubMed Central ID | PMC7106622 |
Grant List | R01 GM099962 / GM / NIGMS NIH HHS / United States T32 AG000255 / AG / NIA NIH HHS / United States |
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