Fig. 3: Systematic modeling of cis- and trans- element temporal interactions reveals discrete regulatory modules spanning erythropoiesis.

a Developmental responses of DHS accessibility and transcription factor expression levels were found to be correlated across the genome. b The density of a given developmental DHS is modeled after the TF binding motif composition and the expression of the binding TFs using elastic-net regression. The model returns a coefficient for each pair of DHS and binding TF which denotes how strongly (positively or negatively) the TF expression is associated with the accessibility of the particular DHS. c Hierarchical clustering of 52 highly connected TFs based on the cosine distances of the regression coefficient from 11,734 DHS reveals 5 clusters of developmentally regulated TFs. Transcription factors along with their positively associated DHS comprise a regulatory module (modules 1–5). d The fraction of DHS per cluster positively associated with a TF identifies the major drivers of chromatin accessibility during erythropoiesis.