Genome-wide association between transcription factor expression and chromatin accessibility reveals chromatin state regulators

To better understand genome regulation, it is important to uncover the role of transcription factors in the process of chromatin structure establishment and maintenance. Here we present a data-driven approach to systematically characterize transcription factors that are relevant for this process. Our method uses a linear mixed modeling approach to combine data sets of transcription factor binding motif enrichments in open chromatin and gene expression across the same set of cell lines. Applying this approach to the ENCODE data set we confirm already known and imply numerous novel transcription factors in playing a role in the establishment or maintenance of open chromatin.