ArticleMolecular cell2020
Robust Hi-C Maps of Enhancer-Promoter Interactions Reveal the Function of Non-coding Genome in Neural Development and Diseases.
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Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 2 of them syntheses that pooled it.
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106citing papers in PubMed, 2 pooled it
9.5field-weighted citation impact, top 1% of its field
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Who cites it
106 citing papers in PubMed, 2 syntheses or guidelines pooled it, 185 citations in OpenAlex.
- Cross-platform Hi-C meta-analysis identifies functional insulators that actively block enhancer-promoter interactions.Nature communications · 2026Pooled it
- Extended genome-wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Pooled it
- Spatially resolved chromatin architectures in mammalian brain tissues.Nature methods · 2026Article
- LAWS-HiC: A Locally Adaptive Weighting and Screening (LAWS) Approach to Improve Detection of Long-Range Chromatin Interactions from Hi-C Data.Methods and protocols · 2026Article
- HiC2Self: Self-supervised denoising for bulk and single-cell Hi-C contact maps.Science advances · 2026Article
- Rapid reduction in global chromatin loop size after acute STAG2 reconstitution in human cancer cells.bioRxiv : the preprint server for biology · 2026Article
- Chromatin-associated intronic RNAs from long genes form introsomes that shape nuclear architecture in neuronal cells.bioRxiv : the preprint server for biology · 2026Article
- Whole-genome 3D architectural screen reveals modulators of brain DNA structure.bioRxiv : the preprint server for biology · 2026Article
- 3D genetic architecture of schizophrenia risk across three neuronal subtypes.Molecular psychiatry · 2026Article
- Chromatin spatial analysis by METALoci unveils sex-determining 3D regulatory hubs.Nature structural & molecular biology · 2026Article
- Genetic correlation analysis of Alzheimer's disease and stroke implicates PHLPP1 as a shared locus in individuals of African ancestry.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- The adenovirus oncoprotein E1B-55K reshapes epigenetic histone modifications in primary human cells.mBio · 2026Article
- Enhanced Hi-C Capture Analysis reveals complex regulatory architecture at thebioRxiv : the preprint server for biology · 2026Article
- Boosting the detection of enhancer-promoter loops via normalization methods for chromatin interaction data.Nature communications · 2026Article
- An ancient genome duplication event drives the development and evolution of spinnerets in spiders.Science advances · 2026Article
- Analysis of chromatin structure reveals the connection between sQTLs and the splicing of distant genes.Scientific reports · 2025Article
- Local genetic correlation analysis of Alzheimer's disease and stroke implicatesmedRxiv : the preprint server for health sciences · 2025Article
- Pathogenicity of Mediator Complex Subunit 27 (MED27) in a Neurodevelopmental Disorder with Cerebellar Atrophy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Excessive DNA Double-Strand Breaks-Associated 3D Genome Reorganization Contributes to Neural Tube Defects with Folate Deficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A combined genomic arrhythmia propensity score delineates cumulative risk.Cell reports. Medicine · 2025Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 9 institutions in 3 countries.
Leina LuDepartment of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Xiaoxiao LiuDepartment of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Wei-Kai HuangDepartment of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Graduate Program in Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Paola Giusti-RodríguezDepartment of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
Jian CuiDepartment of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Shanshan ZhangDepartment of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Wanying XuDepartment of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Zhexing WenDepartments of Psychiatry and Behavioral Sciences, Cell Biology, and Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Shufeng MaCancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Jonathan D RosenDepartment of Biostatistics, Department of Computer Science, University of North Carolina, Chapel Hill, NC 27599, USA.
Zheng XuDepartment of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Biostatistics, Department of Computer Science, University of North Carolina, Chapel Hill, NC 27599, USA.
Cynthia F BartelsDepartment of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Riki KawaguchiDepartment of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Ming HuDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Peter C ScacheriDepartment of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Zhili RongCancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Dermatology Hospital, Southern Medical University, Guangzhou, 510091, China.
Yun LiDepartment of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Biostatistics, Department of Computer Science, University of North Carolina, Chapel Hill, NC 27599, USA.
Patrick F SullivanDepartment of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Psychiatry, University of North Carolina, Chapel Hill, NC 27599, USA; Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm 171 77, Sweden.
Hongjun SongDepartment of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; The Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Guo-Li MingDepartment of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Graduate Program in Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: gming@pennmedicine.upenn.edu.
Yan LiDepartment of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; College of Graduate Studies, Cleveland State University, Cleveland, OH 44115, USA. Electronic address: yxl1379@case.edu.
Fulai JinDepartment of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Computer and Data Sciences, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: fxj45@case.edu.
Case Western Reserve University · USUniversity of North Carolina at Chapel Hill · USJohns Hopkins University · USSouthern Medical University · CNCalifornia Institute for Regenerative Medicine · USCleveland Clinic · USCleveland State University · USEmory University · USUniversity of California, Los Angeles · US
Funding
Inherited colorectal cancer risk variants: from association to biologyR01CA143237 · NCI · UNIVERSITY OF VIRGINIA · PI CASEY, GRAHAM · 2010 to 2020
$8.4MModeling Zika virus pathogenesis and potential intervention during neural development using a human brain organoid systemU19AI131130 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BRINTON, MARGO A · 2017 to 2021
$7.7MContinuous Neurogenesis in the Mammalian HippocampusR35NS116843 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI HONGJUN SONG · 2020 to 2026
$6.9MFunctional roles of genetic risk factors for brain disorders in neurogenesis and neurodevelopmentR35NS097370 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI MING, GUO-LI · 2017 to 2024
$6.7MRobust mapping of chromatin loops from sparse or single cell Hi-C data with DeepLoopR01HG009658 · NHGRI · CASE WESTERN RESERVE UNIVERSITY · PI Fulai Jin · 2017 to 2026
$5.1MTranslational models of neurodevelopmental epigenetics and disease using human iPSCsP01NS097206 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI SONG, HONGJUN · 2016 to 2020
$4.3MElucidating human beta cell transcriptional regulome with low-input genomic technologiesR01DK113185 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI Yan Li · 2018 to 2026
$4.0MThe role of gene enhancer elements in colon cancerR01CA160356 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI TESAR, PAUL JOSEPH · 2012 to 2023
$3.6MBiology of Colorectal Cancer Risk EnhancersR01CA204279 · NCI · UNIVERSITY OF VIRGINIA · PI CASEY, GRAHAM, SCACHERI, PETER CHRISTOPHER · 2016 to 2020
$3.0MLocal circuitry mechanisms regulating adult hippocampal neurogenesisR37NS047344 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI SONG, HONGJUN · 2013 to 2019
$2.9MSTAG2 mutations and 3D genome organization in glioblastoma multiformeR01CA267872 · NCI · GEORGETOWN UNIVERSITY · PI Fulai Jin, TODD A WALDMAN · 2022 to 2026
$2.7MUnderstanding the variation of induced β-cell differentiation.R01DK131437 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI JIN, FULAI, LI, YAN · 2022 to 2025
$2.4MNCI NIH HHS R01 CA143237NCI NIH HHS R01 CA160356NCI NIH HHS R01 CA204279NCI NIH HHS R01 CA267872NHGRI NIH HHS R01 HG009658NIAID NIH HHS U19 AI131130NIDDK NIH HHS R01 DK113185NIDDK NIH HHS R01 DK131437NIMH NIH HHS K01 MH109772NIMH NIH HHS R01 MH105128NINDS NIH HHS P01 NS097206NINDS NIH HHS R35 NS097370NINDS NIH HHS R35 NS116843NINDS NIH HHS R37 NS047344
Abstract
Genome-wide mapping of chromatin interactions at high resolution remains experimentally and computationally challenging. Here we used a low-input "easy Hi-C" protocol to map the 3D genome architecture in human neurogenesis and brain tissues and also demonstrated that a rigorous Hi-C bias-correction pipeline (HiCorr) can significantly improve the sensitivity and robustness of Hi-C loop identification at sub-TAD level, especially the enhancer-promoter (E-P) interactions. We used HiCorr to compare the high-resolution maps of chromatin interactions from 10 tissue or cell types with a focus on neurogenesis and brain tissues. We found that dynamic chromatin loops are better hallmarks for cellular differentiation than compartment switching. HiCorr allowed direct observation of cell-type- and differentiation-specific E-P aggregates spanning large neighborhoods, suggesting a mechanism that stabilizes enhancer contacts during development. Interestingly, we concluded that Hi-C loop outperforms eQTL in explaining neurological GWAS results, revealing a unique value of high-resolution 3D genome maps in elucidating the disease etiology.
Indexed as
Enhancer Elements, GeneticGene Expression Regulation, DevelopmentalGene Regulatory NetworksGenome, HumanPromoter Regions, GeneticAdultCell LineCerebrumChromatinChromosome MappingFetusHistonesHumansInduced Pluripotent Stem CellsNerve Tissue ProteinsNeural Stem CellsChromatinHistonesNerve Tissue ProteinsTranscription Factorsbias correctionchromatin loopeHi-Cenhancer-promoter interactionGWASHi-CHiCorrneurogenesistranscription regulation
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