Genome Architecture Leads a Bifurcation in Cell Identity

Genome architecture is important in transcriptional regulation, but its dynamics and role during reprogramming are not well understood. Over a time course, we captured genome-wide architecture and transcription during MYOD1-mediated reprogramming of human fibroblasts into the myogenic lineage. We found that chromatin reorganization occurred prior to significant transcriptional changes marking activation of the myogenic program. A global bifurcation event delineated the transition into a myogenic cell identity 32 hours after exogenous MYOD1 activation, an event also reflected in the local dynamics of endogenous MYOD1 and MYOG. These data support a model in which master regulators induce lineage-specific nuclear architecture prior to fulfilling a transcriptional role. Interestingly, early in reprogramming, circadian genes that are MYOD1 targets synchronized their expression patterns. After the bifurcation, myogenic transcription factors that are MYOG targets synchronized their expression, suggesting a cell-type specific rhythm. These data support roles for MYOD1 and MYOG in entraining biological rhythms.