NOMe-HiC: joint profiling of genetic variant, DNA methylation, chromatin accessibility, and 3D genome in the same DNA molecule

Hailu Fu, Haizi Zheng, Xiaoting Chen, Matthew T. Weirauch, Louis J. Muglia, Li Wang*, Yaping Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Cis-regulatory elements are coordinated to regulate the expression of their targeted genes. However, the joint measurement of cis-regulatory elements’ activities and their interactions in spatial proximity is limited by the current sequencing approaches. We describe a method, NOMe-HiC, which simultaneously captures single-nucleotide polymorphisms, DNA methylation, chromatin accessibility (GpC methyltransferase footprints), and chromosome conformation changes from the same DNA molecule, together with the transcriptome, in a single assay. NOMe-HiC shows high concordance with state-of-the-art mono-omic assays across different molecular measurements and reveals coordinated chromatin accessibility at distal genomic segments in spatial proximity and novel types of long-range allele-specific chromatin accessibility.

Original languageEnglish (US)
Article number50
JournalGenome biology
Volume24
Issue number1
DOIs
StatePublished - Dec 2023

Funding

The authors thank Drs. Guoqiang Li and Bing Ren from the Ludwig Institute for Cancer Research and the University of California at San Diego, Dr. Fides Lay from Amgen Inc., and Dr. Raphael Kopan from Cincinnati Children’s Hospital Medical Center for helpful input. The authors also acknowledge the computational support from the Biomedical Informatics (BMI) high-performance computing cluster in CCHMC. The authors thank Drs. Guoqiang Li and Bing Ren from the Ludwig Institute for Cancer Research and the University of California at San Diego, Dr. Fides Lay from Amgen Inc., and Dr. Raphael Kopan from Cincinnati Children’s Hospital Medical Center for helpful input. The authors also acknowledge the computational support from the Biomedical Informatics (BMI) high-performance computing cluster in CCHMC. The review history is available as Additional file 3. Tim Sands was the primary editor of this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

Keywords

  • 3D genome
  • Chromatin accessibility
  • Chromosome conformation changes
  • Cis-regulatory elements
  • Coordinated GpC methyltransferase footprints
  • DNA methylation
  • GpC methyltransferase footprints
  • Joint profiling
  • Long-range allelic-specific CRE activity
  • transcriptome

ASJC Scopus subject areas

  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Cell Biology

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