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  1. Article ; Online: Disorder-based T cell developmental order.

    Liu, Shuai / Zhao, Keji

    Nature immunology

    2024  Volume 24, Issue 10, Page(s) 1602–1603

    Language English
    Publishing date 2024-02-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-023-01623-w
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    Zs.A 5294: Show issues Location:
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    Zs.MG 42: Show issues

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  2. Article ; Online: Reactivating antitumor immunity by inhibiting JMJD1C.

    Wang, Xuezheng / Zhao, Keji

    Nature immunology

    2024  Volume 25, Issue 3, Page(s) 390–391

    Language English
    Publishing date 2024-02-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-024-01760-w
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  3. Article ; Online: Analysis of Chromatin Interaction and Accessibility by Trac-Looping.

    Liu, Shuai / Tang, Qingsong / Zhao, Keji

    Methods in molecular biology (Clifton, N.J.)

    2023  Volume 2611, Page(s) 85–97

    Abstract: Spatial organization of the genome modulates pivotal biological processes. The emerging new technologies have provided novel insights into genome structure and its role in regulating cell activities. To examine the genome-wide chromatin interactions at ... ...

    Abstract Spatial organization of the genome modulates pivotal biological processes. The emerging new technologies have provided novel insights into genome structure and its role in regulating cell activities. To examine the genome-wide chromatin interactions at accessible chromatin regions, we developed a DNA transposase-mediated analysis of chromatin looping (Trac-looping) method for simultaneously detecting chromatin interactions and chromatin accessibility. Here, we describe a detailed protocol of generating Trac-looping libraries.
    MeSH term(s) Chromatin ; Chromosomes ; Genome
    Chemical Substances Chromatin
    Language English
    Publishing date 2023-02-21
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2899-7_7
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  4. Article ; Online: The Toolbox for Untangling Chromosome Architecture in Immune Cells.

    Liu, Shuai / Zhao, Keji

    Frontiers in immunology

    2021  Volume 12, Page(s) 670884

    Abstract: The code of life is not only encrypted in the sequence of DNA but also in the way it is organized into chromosomes. Chromosome architecture is gradually being recognized as an important player in regulating cell activities (e.g., controlling ... ...

    Abstract The code of life is not only encrypted in the sequence of DNA but also in the way it is organized into chromosomes. Chromosome architecture is gradually being recognized as an important player in regulating cell activities (e.g., controlling spatiotemporal gene expression). In the past decade, the toolbox for elucidating genome structure has been expanding, providing an opportunity to explore this under charted territory. In this review, we will introduce the recent advancements in approaches for mapping spatial organization of the genome, emphasizing applications of these techniques to immune cells, and trying to bridge chromosome structure with immune cell activities.
    MeSH term(s) Animals ; Chromatin/genetics ; Chromosomes/genetics ; DNA/genetics ; Gene Expression Regulation ; Genome ; Humans ; Immunity, Cellular
    Chemical Substances Chromatin ; DNA (9007-49-2)
    Language English
    Publishing date 2021-04-29
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.670884
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  5. Article ; Online: Hi-TrAC detects active sub-TADs and reveals internal organizations of super-enhancers.

    Cao, Yaqiang / Liu, Shuai / Cui, Kairong / Tang, Qingsong / Zhao, Keji

    Nucleic acids research

    2023  Volume 51, Issue 12, Page(s) 6172–6189

    Abstract: The spatial folding of eukaryotic genome plays a key role in genome function. We report here that our recently developed method, Hi-TrAC, which specializes in detecting chromatin loops among accessible genomic regions, can detect active sub-TADs with a ... ...

    Abstract The spatial folding of eukaryotic genome plays a key role in genome function. We report here that our recently developed method, Hi-TrAC, which specializes in detecting chromatin loops among accessible genomic regions, can detect active sub-TADs with a median size of 100 kb, most of which harbor one or two cell specifically expressed genes and regulatory elements such as super-enhancers organized into nested interaction domains. These active sub-TADs are characterized by highly enriched histone mark H3K4me1 and chromatin-binding proteins, including Cohesin complex. Deletion of selected sub-TAD boundaries have different impacts, such as decreased chromatin interaction and gene expression within the sub-TADs or compromised insulation between the sub-TADs, depending on the specific chromatin environment. We show that knocking down core subunit of the Cohesin complex using shRNAs in human cells or decreasing the H3K4me1 modification by deleting the H3K4 methyltransferase Mll4 gene in mouse Th17 cells disrupted the sub-TADs structure. Our data also suggest that super-enhancers exist as an equilibrium globule structure, while inaccessible chromatin regions exist as a fractal globule structure. In summary, Hi-TrAC serves as a highly sensitive and inexpensive approach to study dynamic changes of active sub-TADs, providing more explicit insights into delicate genome structures and functions.
    MeSH term(s) Animals ; Humans ; Mice ; Chromatin ; Chromatin Assembly and Disassembly ; Genome ; Regulatory Sequences, Nucleic Acid ; Enhancer Elements, Genetic ; Genetic Techniques
    Chemical Substances Chromatin
    Language English
    Publishing date 2023-05-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkad378
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  6. Article ; Online: The epigenetic basis of cellular heterogeneity.

    Carter, Benjamin / Zhao, Keji

    Nature reviews. Genetics

    2020  Volume 22, Issue 4, Page(s) 235–250

    Abstract: Single-cell sequencing-based methods for profiling gene transcript levels have revealed substantial heterogeneity in expression levels among morphologically indistinguishable cells. This variability has important functional implications for tissue ... ...

    Abstract Single-cell sequencing-based methods for profiling gene transcript levels have revealed substantial heterogeneity in expression levels among morphologically indistinguishable cells. This variability has important functional implications for tissue biology and disease states such as cancer. Mapping of epigenomic information such as chromatin accessibility, nucleosome positioning, histone tail modifications and enhancer-promoter interactions in both bulk-cell and single-cell samples has shown that these characteristics of chromatin state contribute to expression or repression of associated genes. Advances in single-cell epigenomic profiling methods are enabling high-resolution mapping of chromatin states in individual cells. Recent studies using these techniques provide evidence that variations in different aspects of chromatin organization collectively define gene expression heterogeneity among otherwise highly similar cells.
    MeSH term(s) Cell Lineage/genetics ; Chromatin/genetics ; Computational Biology ; DNA Methylation/genetics ; Epigenesis, Genetic/genetics ; Genetic Heterogeneity ; Histones/genetics ; Humans ; Promoter Regions, Genetic/genetics ; Regulatory Sequences, Nucleic Acid/genetics ; Sequence Analysis, DNA
    Chemical Substances Chromatin ; Histones
    Language English
    Publishing date 2020-11-26
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Review
    ZDB-ID 2035157-4
    ISSN 1471-0064 ; 1471-0056
    ISSN (online) 1471-0064
    ISSN 1471-0056
    DOI 10.1038/s41576-020-00300-0
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    Zs.A 5474: Show issues Location:
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    Zs.MG 40: Show issues

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  7. Article ; Online: Hi-TrAC reveals division of labor of transcription factors in organizing chromatin loops.

    Liu, Shuai / Cao, Yaqiang / Cui, Kairong / Tang, Qingsong / Zhao, Keji

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 6679

    Abstract: The three-dimensional genomic structure plays a critical role in gene expression, cellular differentiation, and pathological conditions. It is pivotal to elucidate fine-scale chromatin architectures, especially interactions of regulatory elements, to ... ...

    Abstract The three-dimensional genomic structure plays a critical role in gene expression, cellular differentiation, and pathological conditions. It is pivotal to elucidate fine-scale chromatin architectures, especially interactions of regulatory elements, to understand the temporospatial regulation of gene expression. In this study, we report Hi-TrAC as a proximity ligation-free, robust, and sensitive technique to profile genome-wide chromatin interactions at high-resolution among regulatory elements. Hi-TrAC detects chromatin looping among accessible regions at single nucleosome resolution. With almost half-million identified loops, we reveal a comprehensive interaction network of regulatory elements across the genome. After integrating chromatin binding profiles of transcription factors, we discover that cohesin complex and CTCF are responsible for organizing long-range chromatin loops, related to domain formation; whereas ZNF143 and HCFC1 are involved in structuring short-range chromatin loops between regulatory elements, which directly regulate gene expression. Thus, we introduce a methodology to identify a delicate and comprehensive network of cis-regulatory elements, revealing the complexity and a division of labor of transcription factors in organizing chromatin loops for genome organization and gene expression.
    MeSH term(s) Transcription Factors/genetics ; Transcription Factors/metabolism ; Chromatin/genetics ; Chromosomes/metabolism ; Regulatory Sequences, Nucleic Acid ; Genome ; CCCTC-Binding Factor/genetics ; CCCTC-Binding Factor/metabolism
    Chemical Substances Transcription Factors ; Chromatin ; CCCTC-Binding Factor
    Language English
    Publishing date 2022-11-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-34276-8
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  8. Article: CTCF and cellular heterogeneity.

    Ren, Gang / Zhao, Keji

    Cell & bioscience

    2019  Volume 9, Page(s) 83

    Abstract: Cellular heterogeneity, which was initially defined for tumor cells, is a fundamental property of all cellular systems, ranging from genetic diversity to cell-to-cell variation driven by stochastic molecular interactions involved all cellular processes. ... ...

    Abstract Cellular heterogeneity, which was initially defined for tumor cells, is a fundamental property of all cellular systems, ranging from genetic diversity to cell-to-cell variation driven by stochastic molecular interactions involved all cellular processes. Different cells display substantial variation in gene expression and in response to environmental signaling even in an apparently homogeneous population of cells. Recent studies started to reveal the underlying mechanisms for cellular heterogeneity, particularly related to the states of chromatin. Accumulating evidence suggests that CTCF, an important factor regulating chromatin organization, plays a key role in the control of gene expression variation by stabilizing enhancer-promoter interaction.
    Language English
    Publishing date 2019-10-11
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2593367-X
    ISSN 2045-3701
    ISSN 2045-3701
    DOI 10.1186/s13578-019-0347-2
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  9. Article: The

    Vidaurre, Velinda / Song, Annabelle / Li, Taibo / Ku, Wai Lim / Zhao, Keji / Qian, Jiang / Chen, Xin

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Many cell types come from tissue-specific adult stem cells that maintain the balance between proliferation and differentiation. Here, we study how the H3K4me3 methyltransferase, Set1, regulates early-stage male germ cell proliferation and differentiation ...

    Abstract Many cell types come from tissue-specific adult stem cells that maintain the balance between proliferation and differentiation. Here, we study how the H3K4me3 methyltransferase, Set1, regulates early-stage male germ cell proliferation and differentiation in
    Language English
    Publishing date 2024-02-14
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.14.580277
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  10. Article: Concurrent mapping of multiple epigenetic marks and co-occupancy using ACT2-seq.

    Carter, Benjamin / Ku, Wai Lim / Pelt, Joe / Zhao, Keji

    Cell & bioscience

    2021  Volume 11, Issue 1, Page(s) 198

    Abstract: Background: Genome-wide profiling of epigenetic marks is a core technology in molecular genetics. Co-occupancy of different epigenetic marks or protein factors at the same genomic locations must often be inferred from multiple independently collected ... ...

    Abstract Background: Genome-wide profiling of epigenetic marks is a core technology in molecular genetics. Co-occupancy of different epigenetic marks or protein factors at the same genomic locations must often be inferred from multiple independently collected data sets. However, this strategy does not provide direct evidence of co-enrichment in the same cells due to the existence of cellular heterogeneity. To address this issue, we have developed a technique termed ACT2-seq that is capable of concurrently profiling multiple epigenetic marks in a single biological sample. In addition to reducing the numbers of samples required for experiments, ACT2-seq is capable of mapping co-occupancy of epigenetic factors on chromatin. This strategy provides direct evidence of co-enrichment without requiring complex single-molecule, single-cell, or magnetic bead-based approaches.
    Results: We concurrently profiled pairs of two epigenetic marks using ACT2-seq as well as three marks in individual samples. Data obtained using ACT2-seq were found to be reproducible and robust. ACT2-seq was capable of cleanly partitioning concurrently mapped data sets that exhibited distinct enrichment patterns. Using ACT2-seq, we identified distinct relationships between co-occupancy of specific histone modifications and gene expression patterns.
    Conclusions: We conclude that ACT2-seq presents an attractive option for epigenomic profiling due to its ease of use, potential for reducing sample and sequencing costs, and ability to simultaneously profile co-occupancy of multiple histone marks and/or chromatin-associated proteins.
    Language English
    Publishing date 2021-12-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 2593367-X
    ISSN 2045-3701
    ISSN 2045-3701
    DOI 10.1186/s13578-021-00711-4
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