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Cis-regulatory logic in the endo16 gene: switching from a specification to a differentiation mode of control

Yuh, Chiou-Hwa and Bolouri, Hamid and Davidson, Eric H. (2001) Cis-regulatory logic in the endo16 gene: switching from a specification to a differentiation mode of control. Development, 128 (5). pp. 617-629. ISSN 0950-1991.

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The endo16 gene of Strongylocentrotus purpuratus encodes a secreted protein of the embryonic and larval midgut. The overall functional organization of the spatial and temporal control system of this gene are relatively well known from a series of earlier cis-regulatory studies. Our recent computational model for the logic operations of the proximal region of the endo16 control system (Module A) specifies the function of interactions at each transcription factor target site of Module A. Here, we extend sequence level functional analysis to the adjacent cis-regulatory region, Module B. The computational logic model is broadened to include B/A interactions as well as other Module B functions. Module B drives expression later in development and its major activator is responsible for a sharp, gut-specific increase in transcription after gastrulation. As shown earlier, Module B output undergoes a synergistic amplification that requires interactions within Module A. The interactions within Module B that are required to generate and transmit its output to Module A are identified. Logic considerations predicted an internal cis-regulatory switch by which spatial control of endo16 expression is shifted from Module A (early) to Module B (later). This prediction was confirmed experimentally and a distinct set of interactions in Module B that mediate the switch function was demonstrated. The endo16 computational model now provides a detailed explanation of the information processing functions executed by the cis-regulatory system of this gene throughout embryogenesis. Early in development the gene participates in the specification events that define the endomesoderm; later it functions as a gut-specific differentiation gene. The cis-regulatory switch mediates this functional change.

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Additional Information:Copyright © 2001 by Company of Biologists. Accepted 4 December 2000; published on WWW 7 February 2001. We are grateful to Prof. Ellen V. Rothenberg for her perspicacious and helpful review of a draft of the manuscript. We are very pleased to acknowledge the support of the Stowers Institute for Medical Research, and of the National Institute of Child Health and Human Development (Grant HD 37105).
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Stowers Institute for Medical ResearchUNSPECIFIED
National Institute of Child Health and Human Development (NICHD)HD 37105
Subject Keywords:Gene regulation, Computational model, Gene transfer, Sea urchin
Issue or Number:5
Record Number:CaltechAUTHORS:YUHdev01
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:12711
Deposited By: Archive Administrator
Deposited On:21 Dec 2008 02:04
Last Modified:03 Oct 2019 00:31

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