Genomic analysis reveals a tight link between transcription factor dynamics and regulatory network architecture

Abstract Although several studies have provided important insights into the general principles of biological networks, the link between network organization and the genome‐scale dynamics of the underlying entities (genes, mRNAs, and proteins) and its role in systems behavior remain unclear. Here we...

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Main Authors: Raja Jothi, S Balaji, Arthur Wuster, Joshua A Grochow, Jörg Gsponer, Teresa M Przytycka, L Aravind, M Madan Babu
Format: Article
Language:English
Published: Springer Nature 2009-08-01
Series:Molecular Systems Biology
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Online Access:https://doi.org/10.1038/msb.2009.52
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author Raja Jothi
S Balaji
Arthur Wuster
Joshua A Grochow
Jörg Gsponer
Teresa M Przytycka
L Aravind
M Madan Babu
author_facet Raja Jothi
S Balaji
Arthur Wuster
Joshua A Grochow
Jörg Gsponer
Teresa M Przytycka
L Aravind
M Madan Babu
author_sort Raja Jothi
collection DOAJ
description Abstract Although several studies have provided important insights into the general principles of biological networks, the link between network organization and the genome‐scale dynamics of the underlying entities (genes, mRNAs, and proteins) and its role in systems behavior remain unclear. Here we show that transcription factor (TF) dynamics and regulatory network organization are tightly linked. By classifying TFs in the yeast regulatory network into three hierarchical layers (top, core, and bottom) and integrating diverse genome‐scale datasets, we find that the TFs have static and dynamic properties that are similar within a layer and different across layers. At the protein level, the top‐layer TFs are relatively abundant, long‐lived, and noisy compared with the core‐ and bottom‐layer TFs. Although variability in expression of top‐layer TFs might confer a selective advantage, as this permits at least some members in a clonal cell population to initiate a response to changing conditions, tight regulation of the core‐ and bottom‐layer TFs may minimize noise propagation and ensure fidelity in regulation. We propose that the interplay between network organization and TF dynamics could permit differential utilization of the same underlying network by distinct members of a clonal cell population.
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issn 1744-4292
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spelling doaj-art-566319d3c18c406dbdba2b134d6b2a972025-08-24T11:59:31ZengSpringer NatureMolecular Systems Biology1744-42922009-08-015111510.1038/msb.2009.52Genomic analysis reveals a tight link between transcription factor dynamics and regulatory network architectureRaja Jothi0S Balaji1Arthur Wuster2Joshua A Grochow3Jörg Gsponer4Teresa M Przytycka5L Aravind6M Madan Babu7Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of HealthBiostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of HealthMRC Laboratory of Molecular BiologyDepartment of Computer Science, University of ChicagoMRC Laboratory of Molecular BiologyNational Center for Biotechnology Information, National Library of Medicine, National Institutes of HealthNational Center for Biotechnology Information, National Library of Medicine, National Institutes of HealthMRC Laboratory of Molecular BiologyAbstract Although several studies have provided important insights into the general principles of biological networks, the link between network organization and the genome‐scale dynamics of the underlying entities (genes, mRNAs, and proteins) and its role in systems behavior remain unclear. Here we show that transcription factor (TF) dynamics and regulatory network organization are tightly linked. By classifying TFs in the yeast regulatory network into three hierarchical layers (top, core, and bottom) and integrating diverse genome‐scale datasets, we find that the TFs have static and dynamic properties that are similar within a layer and different across layers. At the protein level, the top‐layer TFs are relatively abundant, long‐lived, and noisy compared with the core‐ and bottom‐layer TFs. Although variability in expression of top‐layer TFs might confer a selective advantage, as this permits at least some members in a clonal cell population to initiate a response to changing conditions, tight regulation of the core‐ and bottom‐layer TFs may minimize noise propagation and ensure fidelity in regulation. We propose that the interplay between network organization and TF dynamics could permit differential utilization of the same underlying network by distinct members of a clonal cell population.https://doi.org/10.1038/msb.2009.52dynamicshierarchynoisesystems biologytranscription network
spellingShingle Raja Jothi
S Balaji
Arthur Wuster
Joshua A Grochow
Jörg Gsponer
Teresa M Przytycka
L Aravind
M Madan Babu
Genomic analysis reveals a tight link between transcription factor dynamics and regulatory network architecture
Molecular Systems Biology
dynamics
hierarchy
noise
systems biology
transcription network
title Genomic analysis reveals a tight link between transcription factor dynamics and regulatory network architecture
title_full Genomic analysis reveals a tight link between transcription factor dynamics and regulatory network architecture
title_fullStr Genomic analysis reveals a tight link between transcription factor dynamics and regulatory network architecture
title_full_unstemmed Genomic analysis reveals a tight link between transcription factor dynamics and regulatory network architecture
title_short Genomic analysis reveals a tight link between transcription factor dynamics and regulatory network architecture
title_sort genomic analysis reveals a tight link between transcription factor dynamics and regulatory network architecture
topic dynamics
hierarchy
noise
systems biology
transcription network
url https://doi.org/10.1038/msb.2009.52
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