Genome Architecture Mediates Transcriptional Control of Human Myogenic Reprogramming

Genome architecture has emerged as a critical element of transcriptional regulation, although its role in the control of cell identity is not well understood. Here we use transcription factor (TF)-mediated reprogramming to examine the interplay between genome architecture and transcriptional program...

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Veröffentlicht in:iScience Jg. 6; S. 232 - 246
Hauptverfasser: Liu, Sijia, Chen, Haiming, Ronquist, Scott, Seaman, Laura, Ceglia, Nicholas, Meixner, Walter, Chen, Pin-Yu, Higgins, Gerald, Baldi, Pierre, Smale, Steve, Hero, Alfred, Muir, Lindsey A., Rajapakse, Indika
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Elsevier Inc 31.08.2018
Elsevier
Schlagworte:
Integrative Aspects of Cell Biology
Molecular Structure
Omics
Systems Biology
Molecular Structure
Systems Biology
Integrative Aspects of Cell Biology
Omics
ISSN:2589-0042, 2589-0042
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Zusammenfassung:Genome architecture has emerged as a critical element of transcriptional regulation, although its role in the control of cell identity is not well understood. Here we use transcription factor (TF)-mediated reprogramming to examine the interplay between genome architecture and transcriptional programs that transition cells into the myogenic identity. We recently developed new methods for evaluating the topological features of genome architecture based on network centrality. Through integrated analysis of these features of genome architecture and transcriptome dynamics during myogenic reprogramming of human fibroblasts we find that significant architectural reorganization precedes activation of a myogenic transcriptional program. This interplay sets the stage for a critical transition observed at several genomic scales reflecting definitive adoption of the myogenic phenotype. Subsequently, TFs within the myogenic transcriptional program participate in entrainment of biological rhythms. These findings reveal a role for topological features of genome architecture in the initiation of transcriptional programs during TF-mediated human cellular reprogramming. [Display omitted] •4D Nucleome analysis of direct human fibroblast to muscle reprogramming•A space-time bifurcation marks transit to a new cell identity•Chromatin reorganization precedes significant transcriptional changes•Myogenic master regulators have a role in entraining biological rhythms Molecular Structure; Integrative Aspects of Cell Biology; Systems Biology; Omics
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These authors contributed equally
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2018.08.002