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      Detect accessible chromatin using ATAC-sequencing, from principle to applications

      review-article
      , ,
      Hereditas
      BioMed Central
      Chromatin accessibility, Tn5 transposase, ATAC-seq, Promoter, Enhancer

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          Abstract

          Background

          Chromatin accessibility is crucial for gene expression regulation in specific cells and in multiple biological processes. Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) is an effective way to reveal chromatin accessibility at a genome-wide level. Through ATAC-seq, produced reads from a small number of cells reflect accessible regions that correspond to nucleosome positioning and transcription factor binding sites, due to probing hyperactive Tn5 transposase to DNA sequence.

          Conclusion

          In this review, we summarize both principle and features of ATAC-seq, highlight its applications in basic and clinical research. ATAC-seq has generated comprehensive chromatin accessible maps, and is becoming a powerful tool to understand dynamic gene expression regulation in stem cells, early embryos and tumors.

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          Most cited references82

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          Transcriptional control of human p53-regulated genes.

          The p53 protein regulates the transcription of many different genes in response to a wide variety of stress signals. Following DNA damage, p53 regulates key processes, including DNA repair, cell-cycle arrest, senescence and apoptosis, in order to suppress cancer. This Analysis article provides an overview of the current knowledge of p53-regulated genes in these pathways and others, and the mechanisms of their regulation. In addition, we present the most comprehensive list so far of human p53-regulated genes and their experimentally validated, functional binding sites that confer p53 regulation.
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            Conserved roles for murine DUX and human DUX4 in activating cleavage stage genes and MERVL/HERVL retrotransposons

            To better understand transcriptional regulation during human oogenesis and pre-implantation development, we defined stage-specific transcription, which revealed the cleavage stage as highly distinctive. Here, we present multiple lines of evidence that a eutherian-specific, multi-copy retrogene, DUX4, encodes a transcription factor which activates hundreds of endogenous genes (e.g. ZSCAN4, ZFP352, KDM4E) and retroviral elements (MERVL/HERVL-family) that defines the cleavage-specific transcriptional programs in mouse and human. Remarkably, mouse Dux expression is both necessary and sufficient to convert mouse embryonic stem cells into two-cell embryo-like (‘2C-like’) cells, measured here by the reactivation of ‘2C’ genes and repeat elements, the loss of POU5F1 protein and chromocenters, and by the conversion of the chromatin landscape (assessed by ATAC-seq) to a state strongly resembling mouse two-cell embryos. Taken together, we propose mouse DUX and human DUX4 as major drivers of the cleavage/‘2C’ state.
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              Global mapping of protein-DNA interactions in vivo by digital genomic footprinting

              The orchestrated binding of transcriptional activators and repressors to specific DNA sequences in the context of chromatin defines the regulatory program of eukaryotic genomes. We developed a digital approach to assay regulatory protein occupancy on genomic DNA in vivo by dense mapping of individual DNase I cleavages from intact nuclei using massively parallel DNA sequencing. Analysis of > 23 million cleavages across the Saccharomyces cerevisiae genome revealed thousands of protected regulatory protein footprints, enabling de novo derivation of factor binding motifs as well as the identification of hundreds of novel binding sites for major regulators. We observed striking correspondence between nucleotide-level DNase I cleavage patterns and protein-DNA interactions determined by crystallography. The data also yielded a detailed view of larger chromatin features including positioned nucleosomes flanking factor binding regions. Digital genomic footprinting provides a powerful approach to delineate the cis-regulatory framework of any organism with an available genome sequence.
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                Author and article information

                Contributors
                taosun@hqu.edu.cn
                Journal
                Hereditas
                Hereditas
                Hereditas
                BioMed Central (London )
                0018-0661
                1601-5223
                15 August 2019
                15 August 2019
                2019
                : 156
                : 29
                Affiliations
                ISNI 0000 0000 8895 903X, GRID grid.411404.4, Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, , Huaqiao University, ; 668 Jimei Road, Xiamen, 361021 Fujian China
                Article
                105
                10.1186/s41065-019-0105-9
                6696680
                31427911
                62e14654-2c3b-43a4-a623-802293517feb
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 31 May 2019
                : 12 August 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100002858, China Postdoctoral Science Foundation;
                Award ID: 2017M622053
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81471152
                Award ID: 31771141
                Award Recipient :
                Categories
                Review
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                © The Author(s) 2019

                chromatin accessibility,tn5 transposase,atac-seq,promoter,enhancer

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