title: ATAC-see reveals the accessible genome by transposase-mediated imaging and sequencing.
abstract: Spatial organization of the genome plays a central role in gene expression, DNA replication, and repair. But current epigenomic approaches largely map DNA regulatory elements outside of the native context of the nucleus. Here we report assay of transposase-accessible chromatin with visualization (ATAC-see), a transposase-mediated imaging technology that employs direct imaging of the accessible genome in situ, cell sorting, and deep sequencing to reveal the identity of the imaged elements. ATAC-see revealed the cell-type-specific spatial organization of the accessible genome and the coordinated process of neutrophil chromatin extrusion, termed NETosis. Integration of ATAC-see with flow cytometry enables automated quantitation and prospective cell isolation as a function of chromatin accessibility, and it reveals a cell-cycle dependence of chromatin accessibility that is especially dynamic in G1 phase. The integration of imaging and epigenomics provides a general and scalable approach for deciphering the spatiotemporal architecture of gene control.
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, California, USA.
authors.forename: Xingqi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, California, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California, USA.
authors.forename: Will
authors.initials: W
authors.lastname: Draper
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, California, USA.|Department of Genetics, Stanford University, Stanford, California, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Buenrostro
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, California, USA.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Litzenburger
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, California, USA.
authors.forename: Seung Woo
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, California, USA.
authors.forename: Ansuman T
authors.initials: AT
authors.lastname: Satpathy
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, California, USA.
authors.forename: Ava C
authors.initials: AC
authors.lastname: Carter
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California, USA.
authors.forename: Rajarshi P
authors.initials: RP
authors.lastname: Ghosh
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California, USA.|Department of Chemistry, University of California, Berkeley, Berkeley, California, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: East-Seletsky
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California, USA.|Department of Chemistry, University of California, Berkeley, Berkeley, California, USA.|Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California, USA.|Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Doudna
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, California, USA.|Department of Genetics, Stanford University, Stanford, California, USA.|Department of Applied Physics, Stanford University, Stanford, California, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenleaf
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California, USA.
authors.forename: Jan T
authors.initials: JT
authors.lastname: Liphardt
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, California, USA.
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004251:DNA Transposable Elements / Q000235:genetics; D044127:Epigenesis, Genetic; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry*; D015894:Genome, Human; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007091:Image Processing, Computer-Assisted; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000378:metabolism; D013194:Staining and Labeling; D019895:Transposases / Q000235:genetics / Q000378:metabolism*
chemical_list: C521550:Atto590; D002843:Chromatin; D004251:DNA Transposable Elements; D005456:Fluorescent Dyes; D006576:Heterocyclic Compounds, 4 or More Rings; C473503:Tn5 transposase; D019895:Transposases