Uncovering Transcription Factor Modules Using One- and Three-dimensional Analyses*

Transcriptional regulation is a critical mediator of many normal cellular processes, as well as disease progression. Transcription factors (TFs) often co-localize at cis-regulatory elements on the DNA, form protein complexes, and collaboratively regulate gene expression. Machine learning and Bayesian approaches have been used to identify TF modules in a one-dimensional context. However, recent studies using high throughput technologies have shown that TF interactions should also be considered in three-dimensional nuclear space. Here, we describe methods for identifying TF modules and discuss how moving from a one-dimensional to a three-dimensional paradigm, along with integrated experimental and computational approaches, can lead to a better understanding of TF association networks.