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

• Published in: Nature methods Vol. 10; no. 12; pp. 1213 - 1218
• Main Authors: Buenrostro, Jason D, Giresi, Paul G, Zaba, Lisa C, Chang, Howard Y, Greenleaf, William J
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2013; Nature Publishing Group
• Subjects: 631/1647/2210/2211; 631/208/176; 631/208/177; 631/61; Binding sites; Bioinformatics; Biological Microscopy; Biological Techniques; Biomedical Engineering/Biotechnology; CD4-Positive T-Lymphocytes - cytology; Cell Separation; Chromatin; Chromatin - chemistry; Compaction; Computational Biology - methods; Decision making; Deoxyribonucleic acid; Dimerization; DNA; DNA binding proteins; DNA-Binding Proteins - chemistry; Enhancer Elements, Genetic; Epigenetic inheritance; Epigenetics; Epigenomics; Flow Cytometry - methods; Genomics; Humans; Interleukin-2 - genetics; Life Sciences; Methods; Microbiological assay; Nucleosomes - chemistry; Polymerase Chain Reaction - methods; Proteomics; Sensitivity analysis; Transcription Factors - chemistry; Transposons; United States
• ISSN: 1548-7091; 1548-7105; 1548-7105
• DOI: 10.1038/nmeth.2688

ATAC-seq queries the location of open chromatin, the binding of DNA-associated proteins and chromatin compaction at nucleotide resolution. 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.