Genome Architecture Mediates Transcriptional Control of Human Myogenic Reprogramming

Summary: 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 transcriptiona...

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Main Authors: Sijia Liu, Haiming Chen, Scott Ronquist, Laura Seaman, Nicholas Ceglia, Walter Meixner, Pin-Yu Chen, Gerald Higgins, Pierre Baldi, Steve Smale, Alfred Hero, Lindsey A. Muir, Indika Rajapakse
Format: Article
Language:English
Published: Elsevier 2018-08-01
Series:iScience
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004218301147
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author Sijia Liu
Haiming Chen
Scott Ronquist
Laura Seaman
Nicholas Ceglia
Walter Meixner
Pin-Yu Chen
Gerald Higgins
Pierre Baldi
Steve Smale
Alfred Hero
Lindsey A. Muir
Indika Rajapakse
author_facet Sijia Liu
Haiming Chen
Scott Ronquist
Laura Seaman
Nicholas Ceglia
Walter Meixner
Pin-Yu Chen
Gerald Higgins
Pierre Baldi
Steve Smale
Alfred Hero
Lindsey A. Muir
Indika Rajapakse
author_sort Sijia Liu
collection DOAJ
description Summary: 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. : Molecular Structure; Integrative Aspects of Cell Biology; Systems Biology; Omics Subject Areas: Molecular Structure, Integrative Aspects of Cell Biology, Systems Biology, Omics
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spelling doaj.art-70ab296d666943c5b0fb7f2b760d620c2022-12-21T23:01:34ZengElsevieriScience2589-00422018-08-016232246Genome Architecture Mediates Transcriptional Control of Human Myogenic ReprogrammingSijia Liu0Haiming Chen1Scott Ronquist2Laura Seaman3Nicholas Ceglia4Walter Meixner5Pin-Yu Chen6Gerald Higgins7Pierre Baldi8Steve Smale9Alfred Hero10Lindsey A. Muir11Indika Rajapakse12Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109, USADepartment of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USADepartment of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USADepartment of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USADepartment of Computer Science, University of California-Irvine, Irvine, CA 92697, USADepartment of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USAAI Foundations, IBM T. J. Watson Research Center, Yorktown Heights, NY 10598, USADepartment of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USADepartment of Computer Science, University of California-Irvine, Irvine, CA 92697, USADepartment of Mathematics, City University of Hong Kong, Hong Kong 999077, China; Department of Mathematics, University of California, Berkeley, CA 94720, USADepartment of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109, USADepartment of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USADepartment of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Mathematics, University of Michigan, Ann Arbor, MI 48109, USA; Corresponding authorSummary: 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. : Molecular Structure; Integrative Aspects of Cell Biology; Systems Biology; Omics Subject Areas: Molecular Structure, Integrative Aspects of Cell Biology, Systems Biology, Omicshttp://www.sciencedirect.com/science/article/pii/S2589004218301147
spellingShingle Sijia Liu
Haiming Chen
Scott Ronquist
Laura Seaman
Nicholas Ceglia
Walter Meixner
Pin-Yu Chen
Gerald Higgins
Pierre Baldi
Steve Smale
Alfred Hero
Lindsey A. Muir
Indika Rajapakse
Genome Architecture Mediates Transcriptional Control of Human Myogenic Reprogramming
iScience
title Genome Architecture Mediates Transcriptional Control of Human Myogenic Reprogramming
title_full Genome Architecture Mediates Transcriptional Control of Human Myogenic Reprogramming
title_fullStr Genome Architecture Mediates Transcriptional Control of Human Myogenic Reprogramming
title_full_unstemmed Genome Architecture Mediates Transcriptional Control of Human Myogenic Reprogramming
title_short Genome Architecture Mediates Transcriptional Control of Human Myogenic Reprogramming
title_sort genome architecture mediates transcriptional control of human myogenic reprogramming
url http://www.sciencedirect.com/science/article/pii/S2589004218301147
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