Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Multi-omics analysis of chromatin accessibility and interactions with transcriptome by HiCAR

Xiaolin Wei, Yu Xiang, Ruocheng Shan, Derek T Peters, Tongyu Sun, Xin Lin, Wei Li, Yarui Diao
doi: https://doi.org/10.1101/2020.11.02.366062
Xiaolin Wei
1 Department of Cell Biology, Duke Univeristy;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yu Xiang
2 Duke Univeristy;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ruocheng Shan
3 The George Washington University;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Derek T Peters
4 Duke University;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tongyu Sun
2 Duke Univeristy;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xin Lin
4 Duke University;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wei Li
5 Center for Genetic Medicine Research, Center for Cancer and Immunology Research at Children's National Medical Center
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yarui Diao
4 Duke University;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: yarui.diao@duke.edu
  • Abstract
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The long-range interactions of cis-regulatory elements (cREs) play a central role in regulating the spatial-temporal gene expression program of multi-cellular organism. cREs are characterized by the presence of accessible (or open) chromatin, which can be identified at genome-wide scale with assays such as ATAC-seq, DHS-seq, and FAIRE-seq. However, it remains technically challenging to comprehensively identify the long-range physical interactions that occur between cREs, especially in a cost effective manner using low-input samples. Here, we report HiCAR (High-throughput Chromosome conformation capture on Accessible DNA with mRNA-seq co-assay), a method that enables simultaneous assessment of cis-regulatory chromatin interactions and chromatin accessibility, as well as evaluation of the transcriptome, which represents the functional output of chromatin structure and accessibility. Unlike immunoprecipitation-based methods such as HiChIP, PLAC-seq, and ChIA-PET, HiCAR does not require target-specific antibodies and thus can comprehensively capture the cis-regulatory chromatin contacts anchored at accessible regulatory DNA regions and associated with diverse epigenetic modifications and transcription factor binding. Compared to Trac-looping, another method designed to capture interactions between accessible chromatin regions, HiCAR produced a 17-fold greater yield of informative long-range cis- reads at a similar sequencing depth and required 1,000-fold fewer cells as input. Applying HiCAR to H1 human embryonic stem cells (hESCs) revealed 46,792 cis-regulatory chromatin interactions at 5kb resolution. Interestingly, we found that epigenetically poised, bivalent, and repressed cREs exhibit comparable spatial interaction activity to those transcriptionally activated cREs. Using machine learning approaches, we predicated 22 epigenome features that are potentially important for the spatial interaction activity of cREs in H1 hESC. Lastly, we also identified long-range cis-regulatory chromatin interactions in GM12878 and mouse embryonic stem cells with HiCAR. Our results demonstrate that HiCAR is a robust and cost-effective multi-omics assay, which is broadly applicable for simultaneous analysis of genome architecture, chromatin accessibility, and the transcriptome using low-input samples.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted December 19, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Multi-omics analysis of chromatin accessibility and interactions with transcriptome by HiCAR
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Multi-omics analysis of chromatin accessibility and interactions with transcriptome by HiCAR
Xiaolin Wei, Yu Xiang, Ruocheng Shan, Derek T Peters, Tongyu Sun, Xin Lin, Wei Li, Yarui Diao
bioRxiv 2020.11.02.366062; doi: https://doi.org/10.1101/2020.11.02.366062
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Multi-omics analysis of chromatin accessibility and interactions with transcriptome by HiCAR
Xiaolin Wei, Yu Xiang, Ruocheng Shan, Derek T Peters, Tongyu Sun, Xin Lin, Wei Li, Yarui Diao
bioRxiv 2020.11.02.366062; doi: https://doi.org/10.1101/2020.11.02.366062

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3609)
  • Biochemistry (7590)
  • Bioengineering (5533)
  • Bioinformatics (20833)
  • Biophysics (10347)
  • Cancer Biology (7998)
  • Cell Biology (11663)
  • Clinical Trials (138)
  • Developmental Biology (6619)
  • Ecology (10227)
  • Epidemiology (2065)
  • Evolutionary Biology (13648)
  • Genetics (9557)
  • Genomics (12860)
  • Immunology (7932)
  • Microbiology (19575)
  • Molecular Biology (7678)
  • Neuroscience (42193)
  • Paleontology (309)
  • Pathology (1259)
  • Pharmacology and Toxicology (2208)
  • Physiology (3272)
  • Plant Biology (7064)
  • Scientific Communication and Education (1295)
  • Synthetic Biology (1953)
  • Systems Biology (5435)
  • Zoology (1119)