An automated high-throughput ATAC-seq assay reveals differential transcription factor dosage response of chromatin accessibility

Variations in transcription factor (TF) dosage is implicated in haploinsufficient diseases and drives epigenetic cell fate decisions in development. TFs exert their regulatory function through interacting with the open chromatin. However, it is unclear how variations in TF dosage quantitatively affect the genome-wide chromatin accessibility landscape. To systematically profile the quantitative relationship between TF dosage and open chromatin, we developed an automated high-throughput ATAC-seq assay termed RoboATAC that has demonstrated comparable performance to the gold standard OmniATAC assay. Using RoboATAC, we profiled the chromatin accessibility and gene expression of HEK293T cells overexpressing 5 different TFs at 4 dosages, including both individual TFs and pairwise combinations.