TF co-binding to nucleosome arrays

Cell type maintenance and conversion require the combined action of transcription factors (TFs), but the underlying principles remain elusive. Here, we investigated how four TF combinations lead to different reprogramming outputs by studying TF occupancy, nucleosome positioning, and genome 3D organization. We reveal that TF combinations target nucleosome with distinct 3D nucleosome conformations. We also reveal that TFs employ different motif readout mechanisms to reach their cell type specific targets. Moreover, the ability of pioneer TFs to enable non-pioneer factors the access to closed chromatin is markedly different across combinations. Overall, our findings uncover distinct modes of action for TFs during reprogramming. ChIP-seq of four different TF combinations during early and final reprogramming. Mnase-seq and Micro-C in non-reprogrammed and fully-reprogrammed cells.