Characterization of chromatin accessibility with a transposome hypersensitive sites sequencing (THS-seq) assay

Chromatin accessibility captures in vivo protein-chromosome binding status, and is considered an informative proxy for protein-DNA interactions. DNase I and Tn5 transposase assays require thousands to millions of fresh cells for comprehensive chromatin mapping. Applying Tn5 tagmentation to hundreds of cells results in sparse chromatin maps. We present a transposome hypersensitive sites sequencing assay for highly sensitive characterization of chromatin accessibility. Linear amplification of accessible DNA ends with in vitro transcription, coupled with an engineered Tn5 super-mutant, demonstrates improved sensitivity on limited input materials, and accessibility of small regions near distal enhancers, compared with ATAC-seq. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-0882-7) contains supplementary material, which is available to authorized users.