The Her7 Node Modulates the Network Topology of the Zebrafish Segmentation Clock Via Sequestration of the Hes6 Hub

Overview

Journal Development

Specialty Biology

Date 2012 Jan 27

PMID 22278920

Citations 21

Authors

Anna Trofka

Jamie Schwendinger-Schreck

Tim Brend

William Pontius

Thierry Emonet

Scott A Holley

Affiliations

Soon will be listed here.

Abstract

Using in vitro and in vivo assays, we define a network of Her/Hes dimers underlying transcriptional negative feedback within the zebrafish segmentation clock. Some of the dimers do not appear to be DNA-binding, whereas those dimers that do interact with DNA have distinct preferences for cis regulatory sequences. Dimerization is specific, with Hes6 serving as the hub of the network. Her1 binds DNA only as a homodimer but will also dimerize with Hes6. Her12 and Her15 bind DNA both as homodimers and as heterodimers with Hes6. Her7 dimerizes strongly with Hes6 and weakly with Her15. This network structure engenders specific network dynamics and imparts greater influence to the Her7 node. Computational analysis supports the hypothesis that Her7 disproportionately influences the availability of Hes6 to heterodimerize with other Her proteins. Genetic experiments suggest that this regulation is important for operation of the network. Her7 therefore has two functions within the zebrafish segmentation clock. Her7 acts directly within the delayed negative feedback as a DNA-binding heterodimer with Hes6. Her7 also has an emergent function, independent of DNA binding, in which it modulates network topology via sequestration of the network hub.

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