Transposition of native chromatin for multimodal regulatory analysis and personal epigenomics

By Jason D. Buenrostro, P. Giresi, Lisa C. Zaba, Howard Y. Chang, W.J. Greenleaf. 2013

5,662 citations recorded by the source corpus.

We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500–50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution. We discovered classes of DNA-binding factors that strictly avoided, could tolerate or tended to overlap with nucleosomes. Using ATAC-seq maps of human CD4+ T cells from a proband obtained on consecutive days, we demonstrated the feasibility of analyzing an individual's epigenome on a timescale compatible with clinical decision-making.

Subfields: Immunology, Molecular Biology

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Citations in the corpus

Impact of cytosine methylation on DNA binding specificities of human transcription factors (2017, methodology): “(82) with the following modifications: Cultured cells (70% confluency)were harvested through trypsinization, resuspended into single cells, washed with ice-cold PBS and centrifuged for 5min at 500× g.”
Denoising genome-wide histone ChIP-seq with convolutional neural networks (2016, positive): “We believe that a similar approach can be used in other biological assays, e.g., ATAC-seq and DNase-seq (Buenrostro etal.”
Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015, background): “…is compelling evidence that using DNase hypersensitivity or ATAC-seq data to infer open chromatin, followed by combining transcription factor binding with open chromatin footprinting, can provide a powerful and comprehensive way to identify tissue-specific transcription factor regulation 60,61 .”
Identification of transcription factor binding sites using ATAC-seq (2018, positive): “CTCF is an exceptional TF, which usually binds alone to the DNA and has a tight distance to the next nucleosome (Buenrostro et al. 2013; Vierstra et al. 2014).”
Developmental Relationships of Four Exhausted CD8+ T Cell Subsets Reveals Underlying Transcriptional and Epigenetic Landscape Control Mechanisms (2020, methodology): “To define the epigenetic relationships between these Tex subsets, we next compared the open-chromatin landscape of the four Tex subsets, as well as Teff and Tmem cells, by assay for transposase-accessible chromatin followed by deep sequencing (ATAC-seq) (Buenrostro et al., 2013).”