methyl-ATAC-seq measures DNA methylation at accessible chromatin
- 1Department of Molecular Biology and Genetics, Field of Genetics, Genomics, and Development, Cornell University, Ithaca, New York 14853, USA;
- 2Tri-Institutional Training Program in Computational Biology and Medicine, Cornell University, Ithaca, New York 14853, USA;
- 3College of Agricultural and Life Sciences, Cornell University, Ithaca, New York 14853, USA;
- 4College of Veterinary Medicine, Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853, USA;
- 5College of Agriculture and Life Sciences, Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA
Abstract
Chromatin features are characterized by genome-wide assays for nucleosome location, protein binding sites, three-dimensional interactions, and modifications to histones and DNA. For example, assay for transposase accessible chromatin sequencing (ATAC-seq) identifies nucleosome-depleted (open) chromatin, which harbors potentially active gene regulatory sequences; and bisulfite sequencing (BS-seq) quantifies DNA methylation. When two distinct chromatin features like these are assayed separately in populations of cells, it is impossible to determine, with certainty, where the features are coincident in the genome by simply overlaying data sets. Here, we describe methyl-ATAC-seq (mATAC-seq), which implements modifications to ATAC-seq, including subjecting the output to BS-seq. Merging these assays into a single protocol identifies the locations of open chromatin and reveals, unambiguously, the DNA methylation state of the underlying DNA. Such combinatorial methods eliminate the need to perform assays independently and infer where features are coincident.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.245399.118.
- Received October 22, 2018.
- Accepted May 1, 2019.
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