RT Journal Article
SR Electronic
T1 Genome Architecture Leads a Bifurcation in Cell Identity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 151555
DO 10.1101/151555
A1 Sijia Liu
A1 Haiming Chen
A1 Scott Ronquist
A1 Laura Seaman
A1 Nicholas Ceglia
A1 Walter Meixner
A1 Lindsey A. Muir
A1 Pin-Yu Chen
A1 Gerald Higgins
A1 Pierre Baldi
A1 Steve Smale
A1 Alfred Hero
A1 Indika Rajapakse
YR 2017
UL http://biorxiv.org/content/early/2017/06/19/151555.abstract
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.