An automated ATAC-seq method reveals sequence determinants of transcription factor dose response in the open chromatin.

ABSTRACT: Transcription factor (TF) dosage is a critical determinant of cellular identity. However, the quantitative relationship between TF dosage and its regulation of chromatin accessibility and gene expression remains poorly understood. To address this, we developed RoboATAC, a scalable, automated ATAC-seq platform for high-throughput accessibility profiling. We then systematically profiled genome-wide chromatin accessibility and gene expression changes induced by graded overexpression of 22 TFs in HEK293T cells (246 total samples), observing dose-dependent changes in accessibility and aggregate TF footprints. Modeling accessibility as a function of sequence and chromatin states revealed that DNA sequence alone accurately predicts dosage sensitivity at elements that become accessible, with low-a

SUBMITTER: Liu BB 

PROVIDER: S-EPMC12330524 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature