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Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position

Why this mattered

This paper introduced ATAC-seq, replacing slower, cell-hungry assays for chromatin accessibility with a simple transposase-based method that could profile open chromatin from very small numbers of cells. By using Tn5 transposase to insert sequencing adapters directly into accessible regions of native chromatin, Buenrostro and colleagues made it possible to map regulatory DNA, infer transcription-factor occupancy, and recover nucleosome-positioning information in one comparatively fast workflow. The shift was not only technical convenience: it changed open-chromatin profiling from a specialized, high-input experiment into a broadly usable readout of gene regulation.

What became newly possible was systematic regulatory genomics at scales and sample types that had been difficult for DNase-seq, FAIRE-seq, or ChIP-seq. ATAC-seq could be applied to rare primary cells, clinical material, sorted immune populations, developmental time courses, and perturbation experiments where input DNA was limiting. Because accessibility marks promoters, enhancers, insulators, and other regulatory elements, the method gave researchers a practical way to connect noncoding genome function with cell state, disease association, and transcriptional control.

Its longer-term importance was amplified by single-cell genomics. The same core idea, transposase tagging of accessible chromatin, became the foundation for single-cell ATAC-seq and later multimodal assays that jointly measure chromatin accessibility with RNA, protein, methylation, or lineage information in individual cells. Those descendants helped make regulatory-state maps central to cell atlases, cancer evolution studies, developmental biology, and variant-to-function interpretation. In that sense, the 2013 paper did more than introduce a faster assay; it made chromatin accessibility a scalable, quantitative language for studying cellular identity.

Abstract

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