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Encounters across networks: Windows into principles of genomic regulation

Rothenberg, Ellen V. (2019) Encounters across networks: Windows into principles of genomic regulation. Marine Genomics, 44 . pp. 3-12. ISSN 1874-7787. PMCID PMC6431589. doi:10.1016/j.margen.2019.01.003.

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Gene regulatory networks account for the ability of the genome to program development in complex multi-cellular organisms. Such networks are based on principles of gene regulation by combinations of transcription factors that bind to specific cis-regulatory DNA sites to activate transcription. These cis-regulatory regions mediate logic processing at each network node, enabling progressive increases in organismal complexity with development. Gene regulatory network explanations of development have been shown to account for patterning and cell type diversification in fly and sea urchin embryonic systems, where networks are characterized by fast coupling between transcriptional inputs and changes in target gene transcription rates, and crucial cis-regulatory elements are concentrated relatively close to the protein coding sequences of the target genes, thus facilitating their identification. Stem cell-based development in post-embryonic mammalian systems also depends on gene networks, but differs from the fly and sea urchin systems. First, the number of regulatory elements per gene and the distances between regulatory elements and the genes they control are considerably larger, forcing searches via genome-wide transcription factor binding surveys rather than functional assays. Second, the intrinsic timing of network state transitions can be slowed considerably by the need to undo stem-cell chromatin configurations, which presumably add stability to stem-cell states but retard responses to transcription factor changes during differentiation. The dispersed, partially redundant cis-regulatory systems controlling gene expression and the slow state transition kinetics in these systems already reveal new insights and opportunities to extend understanding of the repertoire of gene networks and regulatory system logic.

Item Type:Article
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URLURL TypeDescription CentralArticle
Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 2019 Published by Elsevier B.V. Received 23 October 2018, Revised 6 January 2019, Accepted 6 January 2019, Available online 17 January 2019. This perspective is dedicated to the memory of Eric H. Davidson and the community of scientific inquiry that he inspired. An extensive literature and conversations with this community over decades contributed to the ideas discussed here. References for many general points in this article could be given only as examples or reviews, and apologies are offered to many additional authors for further citations that are not included. Gene network studies in the author’s group have been supported by grants from the USPHS (R33HL089123, R01HL119102, R01AI095943, and RC2CA148278), the L. A. Garfinkle Memorial Laboratory Fund, the Al Sherman Foundation, and the Albert Billings Ruddock Professorship of Biology.
Funding AgencyGrant Number
Louis A. Garfinkle Memorial Laboratory FundUNSPECIFIED
Al Sherman FoundationUNSPECIFIED
Albert Billings Ruddock ProfessorshipUNSPECIFIED
Subject Keywords:Gene regulatory networks; Cis-regulatory elements; Transcription factor binding; Network response timing; Chromatin; Combinatorial logic
PubMed Central ID:PMC6431589
Record Number:CaltechAUTHORS:20190122-161308867
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Official Citation:Ellen V. Rothenberg, Encounters across networks: Windows into principles of genomic regulation, Marine Genomics, Volume 44, 2019, Pages 3-12, ISSN 1874-7787, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:92404
Deposited By: Tony Diaz
Deposited On:23 Jan 2019 00:15
Last Modified:16 Nov 2021 03:50

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