Mapping histone modifications in low cell number and single cells using antibody-guided chromatin tagmentation (ACT-seq)

Benjamin Carter, Wai Lim Ku, Jee Youn Kang, Gangqing Hu, Jonathan Perrie, Qingsong Tang and Keji Zhao ()
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Benjamin Carter: Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung and Blood Institute, NIH
Wai Lim Ku: Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung and Blood Institute, NIH
Jee Youn Kang: Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung and Blood Institute, NIH
Gangqing Hu: Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung and Blood Institute, NIH
Jonathan Perrie: Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung and Blood Institute, NIH
Qingsong Tang: Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung and Blood Institute, NIH
Keji Zhao: Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung and Blood Institute, NIH

Nature Communications, 2019, vol. 10, issue 1, 1-5

Abstract: Abstract Modern next-generation sequencing-based methods have empowered researchers to assay the epigenetic states of individual cells. Existing techniques for profiling epigenetic marks in single cells often require the use and optimization of time-intensive procedures such as drop fluidics, chromatin fragmentation, and end repair. Here we describe ACT-seq, a streamlined method for mapping genome-wide distributions of histone tail modifications, histone variants, and chromatin-binding proteins in a small number of or single cells. ACT-seq utilizes a fusion of Tn5 transposase to Protein A that is targeted to chromatin by a specific antibody, allowing chromatin fragmentation and sequence tag insertion specifically at genomic sites presenting the relevant antigen. The Tn5 transposase enables the use of an index multiplexing strategy (iACT-seq), which enables construction of thousands of single-cell libraries in one day by a single researcher without the need for drop-based fluidics or visual sorting. We conclude that ACT-seq present an attractive alternative to existing techniques for mapping epigenetic marks in single cells.

Date: 2019
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DOI: 10.1038/s41467-019-11559-1

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