PT  - JOURNAL ARTICLE
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
TI  - Genome Architecture Leads a Bifurcation in Cell Identity
AID  - 10.1101/151555
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 151555
4099  - http://biorxiv.org/content/early/2017/06/19/151555.short
4100  - http://biorxiv.org/content/early/2017/06/19/151555.full
AB  - 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.