ArticleMolecular cell2020
Large DNA Methylation Nadirs Anchor Chromatin Loops Maintaining Hematopoietic Stem Cell Identity.
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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 60 papers.
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60 citing papers in PubMed, 94 citations in OpenAlex.
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- H3K27me3 spreading organizes canonical PRC1 chromatin architecture to regulate developmental programs.Nature genetics · 2026Article
- Polycomb chromatin topology enables long-range enhancer recruitment during craniofacial development.Nature communications · 2026Article
- NanoLoop: A Deep Learning Framework Leveraging Nanopore Sequencing for Chromatin Loop Prediction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Epigenome editing of human hematopoietic stem cells enables sustained and reversible thrombosis prevention.bioRxiv : the preprint server for biology · 2026Article
- Oncogenic activation of EVC/EVC2 defines a therapeutically targetable subset of acute myeloid leukemia.Leukemia · 2026Article
- Unraveling the interplay of DNA methylation and chromosome organization.Biochemical Society transactions · 2025Review
- Pan-cancer 3D genomic analysis revealed extremely long Polycomb loops as the biomarker for sensitivity to Polycomb inhibition.bioRxiv : the preprint server for biology · 2025Article
- Senescence-Associated Chromatin Rewiring Promotes Inflammation and Transposable Element Activation.bioRxiv : the preprint server for biology · 2025Article
- Altered 3D genome reorganization mediates precocious myeloid differentiation of aged hematopoietic stem cells in inflammation.Science China. Life sciences · 2025Article
- Transcription factor networks disproportionately enrich for heritability of blood cell phenotypes.Science (New York, N.Y.) · 2025Article
- On correlative and causal links of replicative epimutations.Trends in genetics : TIG · 2025Review
- Epigenetic modifications in hematopoietic ecosystem: a key tuner from homeostasis to acute myeloid leukemia.Blood science (Baltimore, Md.) · 2024Review
- Transcription factor networks disproportionately enrich for heritability of blood cell phenotypes.bioRxiv : the preprint server for biology · 2024Article
- PRC2-AgeIndex as a universal biomarker of aging and rejuvenation.Nature communications · 2024Article
- Strong association between genomic 3D structure and CRISPR cleavage efficiency.PLoS computational biology · 2024Article
- CUX1 regulates human hematopoietic stem cell chromatin accessibility via the BAF complex.Cell reports · 2024Article
- From compartments to loops: understanding the unique chromatin organization in neuronal cells.Epigenetics & chromatin · 2024Review
- Tet-mediated DNA methylation dynamics affect chromosome organization.Nucleic acids research · 2024Article
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 3 countries.
Xiaotian ZhangStem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA; Center for Epigenetics, Van Andel Institute, Grand Rapids, MI, USA. Electronic address: zxtzhangqian@gmail.com.
Mira JeongStem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
Xingfan HuangThe Center for Genome Architecture, Baylor College of Medicine, Houston, TX, USA; Center for Theoretical Biological Physics & Department of Computer Science, Rice University, Houston, TX, USA.
Xue Qing WangCenter for Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
Xinyu WangInstitute of Biomedical Big Data, Wenzhou Medical University, Wenzhou, China.
Wanding ZhouCenter for Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
Muhammad S ShamimThe Center for Genome Architecture, Baylor College of Medicine, Houston, TX, USA; Medical Student Training Program, Baylor College of Medicine, Houston, TX, USA; Center for Theoretical Biological Physics & Department of Computer Science, Rice University, Houston, TX, USA.
Haley GoreCenter for Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
Pamela HimadewiCenter for Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
Yushuai LiuCenter for Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
Ivan D BochkovThe Center for Genome Architecture, Baylor College of Medicine, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Jaime ReyesStem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Madison DotyMolecular Genetic Technology Program, School of Health Professions, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yung-Hsin HuangStem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA; Developmental Biology Program, Baylor College of Medicine, Houston, TX, USA.
Haiyoung JungStem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA; Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Korea, USA.
Emily HeikampStem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Aviva Presser AidenThe Center for Genome Architecture, Baylor College of Medicine, Houston, TX, USA; Developmental Biology Program, Baylor College of Medicine, Houston, TX, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Wei LiDepartment of Bioinformatics, Biological Chemistry, University of California, Irvine CA, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Jianzhong SuInstitute of Biomedical Big Data, Wenzhou Medical University, Wenzhou, China.
Erez Lieberman AidenThe Center for Genome Architecture, Baylor College of Medicine, Houston, TX, USA; Center for Theoretical Biological Physics & Department of Computer Science, Rice University, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Shanghai Institute for Advanced Immunochemical Studies, Shanghai Tech University, Shanghai, China. Electronic address: erez@erez.com.
Margaret A GoodellStem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA. Electronic address: goodell@bcm.edu.
Baylor College of Medicine · USVan Andel Institute · USKorea Research Institute of Bioscience and Biotechnology · KRRice University · USShanghaiTech University · CNThe University of Texas MD Anderson Cancer Center · USWenzhou Medical University · CN
Funding
Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI DAVID R ROWLEY · 2007 to 2026
$73.9MWnt signaling in muscle stem cell agingP01AG036695 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI THOMAS A. RANDO · 2011 to 2026
$29.3MTissue Analysis & Molecular Imaging CoreP30DK056338 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI Geoffrey A Preidis · 2001 to 2026
$28.3MTranslational Research Support CoreP30ES030285 · NIEHS · BAYLOR COLLEGE OF MEDICINE · PI Cheryl L. Walker · 2019 to 2026
$14.7MHematology Training ProgramT32DK060445 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI GOODELL, MARGARET A. · 2002 to 2023
$8.3MREGULATION OF HEMATOPOIETIC PROGENITORS BY DE NOVO DNA METHYLATIONR01DK092883 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI GOODELL, MARGARET A. · 2012 to 2024
$7.4MDNMT3A in Development of Hematologic MalignanciesR01CA183252 · NCI · BAYLOR COLLEGE OF MEDICINE · PI MARGARET A. GOODELL · 2014 to 2026
$7.1MGENOME WIDE MAPPING OF LOOPS USING IN SITU HI-CUM1HG009375 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI LIEBERMAN-AIDEN, EREZ · 2017 to 2021
$4.7MExploring how the genome folds through proximity ligation and sequencingDP2OD008540 · OD · BROAD INSTITUTE, INC. · PI LIEBERMAN-AIDEN, EREZ · 2011 to 2016
$3.0MTransfer: DNA Methylation Canyons in Human Cancers: Methods, Target Genes and Functional ConsequencesR01CA228140 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI LI, WEI · 2019 to 2023
$2.8MSupplement - Beyond pairwise DNA contacts: exploring higher-order genome structure using proximity ligationU01HL130010 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI LIEBERMAN-AIDEN, EREZ · 2015 to 2019
$2.3MComputational and Experimental Modeling of Epigenetic DNA MethylationR01HG007538 · NHGRI · UNIVERSITY OF CALIFORNIA-IRVINE · PI LI, WEI · 2014 to 2018
$1.9MNCI NIH HHS F99 CA222736NCI NIH HHS K00 CA222736NCI NIH HHS P30 CA125123NCI NIH HHS R01 CA183252NCI NIH HHS R01 CA228140NCRR NIH HHS S10 RR024574NHGRI NIH HHS R01 HG007538NHGRI NIH HHS UM1 HG009375NHLBI NIH HHS U01 HL130010NIA NIH HHS P01 AG036695NIDDK NIH HHS P30 DK056338NIDDK NIH HHS R01 DK092883NIDDK NIH HHS R56 DK092883NIDDK NIH HHS T32 DK060445NIEHS NIH HHS P30 ES030285NIH HHS DP2 OD008540NIH HHS S10 OD023469
Abstract
Higher-order chromatin structure and DNA methylation are implicated in multiple developmental processes, but their relationship to cell state is unknown. Here, we find that large (>7.3 kb) DNA methylation nadirs (termed "grand canyons") can form long loops connecting anchor loci that may be dozens of megabases (Mb) apart, as well as inter-chromosomal links. The interacting loci cover a total of ∼3.5 Mb of the human genome. The strongest interactions are associated with repressive marks made by the Polycomb complex and are diminished upon EZH2 inhibitor treatment. The data are suggestive of the formation of these loops by interactions between repressive elements in the loci, forming a genomic subcompartment, rather than by cohesion/CTCF-mediated extrusion. Interestingly, unlike previously characterized subcompartments, these interactions are present only in particular cell types, such as stem and progenitor cells. Our work reveals that H3K27me3-marked large DNA methylation grand canyons represent a set of very-long-range loops associated with cellular identity.
Indexed as
DNA MethylationCCCTC-Binding FactorCell DifferentiationChromatinEnhancer of Zeste Homolog 2 ProteinEpigenesis, GeneticGene Expression RegulationHematopoietic Stem CellsHistonesHomeodomain ProteinsHumansIn Situ Hybridization, FluorescenceLysineNuclear ProteinsShort Stature Homeobox ProteinSOXB1 Transcription FactorsCCCTC-Binding FactorChromatinCTCF protein, humanEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanHistonesHomeodomain ProteinsHoxA proteinLysineNuclear ProteinsShort Stature Homeobox ProteinSHOX protein, humanSOX2 protein, humanSOXB1 Transcription FactorsTranscription FactorsZIC2 protein, human3D genomicschromosomal loopingCpGDNA methylationDNA methylation canyonhematopoieticPolycombself-renewalstem cells
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