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JGM, SS1, Humans, Multiomics, Epigenome, Chromatin, Regulatory Sequences, Nucleic Acid, Transposases, High-Throughput Nucleotide Sequencing

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Nat Commun. 2023;14(1):213.







Y.R. was the Florine Roux Endowed Chair Professor in Genomics and Computational Biology and was supported by 4D Nucleome (U54 DK107967), ENCODE (UM1 HG009409), HG01125, and Human Frontier Science Program (RGP0039/2017). P.W. and C.-L.W. are supported by the 4D Nucleome (U54 DK107967) and ENCODE (UM1 HG009409) consortia. C.-L.W. and C.Y.N. are supported by National Cancer Institute (P30CA034196 and R33 CA236681). H.C. and C.-L.W. are supported by two R01 grants (GM127531 and HG011253) from the National Institutes of Health. W.J.L. is supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.


Connecting genes to their cis-regulatory elements has been enabled by genome-wide mapping of chromatin interactions using proximity ligation in ChIA-PET, Hi-C, and their derivatives. However, these methods require millions of input cells for high-quality data and thus are unsuitable for many studies when only limited cells are available. Conversely, epigenomic profiling via transposase digestion in ATAC-seq requires only hundreds to thousands of cells to robustly map open chromatin associated with transcription activity, but it cannot directly connect active genes to their distal enhancers. Here, we combine proximity ligation in ChIA-PET and transposase accessibility in ATAC-seq into ChIATAC to efficiently map interactions between open chromatin loci in low numbers of input cells. We validate ChIATAC in Drosophila cells and optimize it for mapping 3D epigenomes in human cells robustly. Applying ChIATAC to primary human T cells, we reveal mechanisms that topologically regulate transcriptional programs during T cell activation.


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