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Modeling DNA Sequence-Based cis-Regulatory Gene Networks

Bolouri, Hamid and Davidson, Eric H. (2002) Modeling DNA Sequence-Based cis-Regulatory Gene Networks. Developmental Biology, 246 (1). pp. 2-13. ISSN 0012-1606. doi:10.1006/dbio.2002.0617. https://resolver.caltech.edu/CaltechAUTHORS:20160121-071017567

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Abstract

Gene network analysis requires computationally based models which represent the functional architecture of regulatory interactions, and which provide directly testable predictions. The type of model that is useful is constrained by the particular features of developmentally active cis-regulatory systems. These systems function by processing diverse regulatory inputs, generating novel regulatory outputs. A computational model which explicitly accommodates this basic concept was developed earlier for the cis-regulatory system of the endo16 gene of the sea urchin. This model represents the genetically mandated logic functions that the system executes, but also shows how time-varying kinetic inputs are processed in different circumstances into particular kinetic outputs. The same basic design features can be utilized to construct models that connect the large number of cis-regulatory elements constituting developmental gene networks. The ultimate aim of the network models discussed here is to represent the regulatory relationships among the genomic control systems of the genes in the network, and to state their functional meaning. The target site sequences of the cis-regulatory elements of these genes constitute the physical basis of the network architecture. Useful models for developmental regulatory networks must represent the genetic logic by which the system operates, but must also be capable of explaining the real time dynamics of cis-regulatory response as kinetic input and output data become available. Most importantly, however, such models must display in a direct and transparent manner fundamental network design features such as intra- and intercellular feedback circuitry; the sources of parallel inputs into each cis-regulatory element; gene battery organization; and use of repressive spatial inputs in specification and boundary formation. Successful network models lead to direct tests of key architectural features by targeted cis-regulatory analysis.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1006/dbio.2002.0617DOIArticle
http://www.sciencedirect.com/science/article/pii/S0012160602906172PublisherArticle
Additional Information:© 2002 Elsevier Science. Received for publication December 18, 2001. Revised February 7, 2002. Accepted February 7, 2002. Available online 23 May 2002. We thank the reviewers of this manuscript, Dr. Jonathan P. Rast, and Prof. Ellen Rothenberg of Caltech. This work was supported by grants from the NIH (GM-61005) to E.H.D. and H.B. and from UK BBSRC (310/BIO12024) to H.B.
Funders:
Funding AgencyGrant Number
NIHGM-61005
Biotechnology and Biological Sciences Research Council (BBSRC)310/BIO12024
Subject Keywords:gene regulatory network; model; endo16 gene; regulatory genomics
Issue or Number:1
DOI:10.1006/dbio.2002.0617
Record Number:CaltechAUTHORS:20160121-071017567
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160121-071017567
Official Citation:Hamid Bolouri, Eric H. Davidson, Modeling DNA Sequence-Based cis-Regulatory Gene Networks, Developmental Biology, Volume 246, Issue 1, 1 June 2002, Pages 2-13, ISSN 0012-1606, http://dx.doi.org/10.1006/dbio.2002.0617. (http://www.sciencedirect.com/science/article/pii/S0012160602906172)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:63817
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:21 Jan 2016 19:13
Last Modified:10 Nov 2021 23:21

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