ATAC-seq is compatible with a number of methods for cell separation and isolation, including cell sorting as well as disruption of intact tissues to cellular suspensions. The method has also worked across many cell types and species. However, the following protocol has been optimized for human lymphoblastoid cells, and provides guidance on modifications to the method that might allow adaptation to different cell types. In general, the method is separated into three separate components: cell lysis, transposition, and amplification. Crosslinking generally reduces library creation efficiency, and therefore we recommend starting with fresh unfixed cells for maximum sensitivity of the methodology.
