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Fitting structure to function in gene regulatory networks

Rothenberg, Ellen V. (2017) Fitting structure to function in gene regulatory networks. History and Philosophy of the Life Sciences, 39 (4). Art. No. 37. ISSN 0391-9714. PMCID PMC5660880. doi:10.1007/s40656-017-0164-z.

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Cascades of transcriptional regulation are the common source of the forward drive in all developmental systems. Increases in complexity and specificity of gene expression at successive stages are based on the collaboration of varied combinations of transcription factors already expressed in the cells to turn on new genes, and the logical relationships between the transcription factors acting and becoming newly expressed from stage to stage are best visualized as gene regulatory networks. However, gene regulatory networks used in different developmental contexts underlie processes that actually operate through different sets of rules, which affect the kinetics, synchronicity, and logical properties of individual network nodes. Contrasting early embryonic development in flies and sea urchins with adult mammalian hematopoietic development from stem cells, major differences are seen in transcription factor dosage dependence, the silencing or damping impacts of repression, and the impact of cellular regulatory history on the parts of the genome that are accessible to transcription factor action in a given cell type. These different features not only affect the kinds of models that can illuminate developmental mechanisms in the respective biological systems, but also reflect the evolutionary needs of these biological systems to optimize different aspects of development.

Item Type:Article
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URLURL TypeDescription ReadCube access CentralArticle
Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 2017 Springer International Publishing AG. First Online: 16 October 2017. I thank members of my group for the use of our unpublished data, and the late Eric H. Davidson for years of inspiring and challenging discussions about gene regulatory logic, gene network inference, and network operating principles. Gene network research in the Rothenberg group was supported by grants from the USPHS, especially R33 HL89123, RC2 CA148278, R01 AI95943, and R01 HL119102. I gratefully acknowledge support from the Albert Billings Ruddock Professorship at Caltech.
Funding AgencyGrant Number
NIHR33 HL89123
NIHRC2 CA148278
NIHR01 AI95943
NIHR01 HL119102
Albert Billings Ruddock ProfessorshipUNSPECIFIED
Issue or Number:4
PubMed Central ID:PMC5660880
Record Number:CaltechAUTHORS:20171017-101505757
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Official Citation:Rothenberg, E.V. HPLS (2017) 39: 37.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:82411
Deposited By: Tony Diaz
Deposited On:17 Oct 2017 20:17
Last Modified:22 Mar 2022 18:01

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