TY - JOUR T1 - Genome Architecture Leads a Bifurcation in Cell Identity JF - bioRxiv DO - 10.1101/151555 SP - 151555 AU - Sijia Liu AU - Haiming Chen AU - Scott Ronquist AU - Laura Seaman AU - Nicholas Ceglia AU - Walter Meixner AU - Lindsey A. Muir AU - Pin-Yu Chen AU - Gerald Higgins AU - Pierre Baldi AU - Steve Smale AU - Alfred Hero AU - Indika Rajapakse Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/06/19/151555.abstract N2 - Genome architecture is important in transcriptional regulation, but its dynamics and role during reprogramming are not well understood. Over a time course, we captured genomewide 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. ER -