ATAC-seq of hESC-CM
The ATAC-seq was performed according to previously published protocol {Corces, 2017 #36}. Briefly For the human left ventricle, 50 mg of snap frozen tissue was cut and homogenized using the MACS homogenizer in cold 1X PBS with protease inhibitors. The homogenate was filtered through the 40 m cell strainer, and 50,000 nuclei were pelleted and processed in a similar fashion to the hESC-CM cells.  For the hESC-CMs, 50,000 cells were pelleted at 500 g for 5 minutes. The cells were resuspended in 100 l ATAC-resuspension buffer containing 0.5% NP40, 0.5 % Tween-20 and 0.01% Digitonin. The cells were left on ice for 5 minutes after which 1 ml of cold ATAC-RSB containing 0.1% Tween 20 was added to wash out the lysis buffer. The nuclei were pelleted at 500 g for 5 minutes, the supernatant was carefully removed and the nuclei were resuspended in 50 l transposition mixture containing 25 l of 2x TD buffer, 16.5 l of PBS, 5 l nuclease free water, 0.5 l of 1% digitonin, 0.5 l of 10% Tween-20 and 2.5 l of transposase (Illumina Tagment DNA enzyme 1, Catalogue number 20034198). The reaction was incubated at 37C for 30 minutes in a thermoshaker with 1000 RPM.After the reaction, DNA was extracted using the NEB Monarch PCR & DNA cleanup kit (Catalogue number T1030L), PCR was performed using the Illumina/Nextera primers after which Ampure XP beads were used for library clean up. The resulting library was sequenced on Nextseq