Ultrafine mapping of chromosome conformation at hundred basepair resolution reveals regulatory genome architecture
Year: 2023
Type: article
Abstract: The resolution limit of chromatin conformation capture methodologies (3Cs) has restrained their application in detection of fine-level chromatin structure mediated by cis-regulatory elements (CREs). Here, we report two 3C-derived methods, Tri-4C and Tri-HiC, which utilize multirestriction enzyme digestions for ultrafine mapping of targeted and genome-wide chromatin interaction, respectively, at up to one hundred basepair resolution. Tri-4C identified CRE loop interaction networks and quantitatively revealed their alterations underlying dynamic gene control. Tri-HiC uncovered global fine-gauge regulatory interaction networks, identifying >20-fold more enhancer:promoter (E:P) loops than in situ Hi-C. In addition to vastly improved identification of subkilobase-sized E:P loops, Tri-HiC also uncovered interaction stripes and contact domain insulation from promoters and enhancers, revealing their loop extrusion behaviors resembling the topologically associating domain boundaries. Tri-4C and Tri-HiC provide robust approaches to achieve the high-resolution interactome maps required for characterizing fine-gauge regulatory chromatin interactions in analysis of development, homeostasis, and disease.
Authors: Yizhou Zhu, Michael G. Rosenfeld, Yousin Suh
Institutions: Columbia University, University of California San Diego
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funders: Simons Foundation, Glenn Foundation for Medical Research, Echo Foundation, Buck Institute for Research on Aging, Fondation pour la Recherche Médicale, National Institutes of Health, National Institute on Aging, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: New Methods to Uncover Global Transcriptional Programs for Disease Risk Variants, Combinatorial regulation of the enhancer codes in senescence, From in vivo to in vitro heterochronic parabiosis to identify geronic factors, G3063093169, Combinatorial Actions of Genetic Variants and Gender Bias of Alzherimer's Disease, Phase Separation: A New Phase in Decoding Enhancer-dependent Critical Transcriptional Programs by Nuclear Receptors, Regulatory Landscape of the Aging Human Ovary, Systems Modeling of Alzheimers Disease in C. elegans, DNA Repair, Mutations and Cellular Aging, Enhancer-based Immune and Beta Cell Dysregulation Underlying T1D Risk, G9000047526, G9000093672, G9000257608, G9000275637, Genetic variant-based drug discovery targeting conserved pathways of aging, A Multi-scale Atlas of Senescence in Diverse Tissue Types
OpenAlex ID: W4388285059