Compuational analyses of developmental cis-regualtory control systems

Abstract

Developmental processes are hardwired in the genomic DNA of each animal species. The DNA sequences that specify the architecture of developmental control networks are the cis-regulatory elements that individually determine the state of activity of each of the many genes required to generate a developmental event. These elements each mediate many interactions with transcription factors, which are selected with high specificity according to the target binding sites in each cis-regulatory element. Cis-regulatory elements can be thought of as analog information processing devices. This concept is illustrated by an experimental and computational analysis of a cis-regulatory system from the developmentally regulated Endo 16 gene of the sea urchin embryo. Large-scale developmental events require mobilization of batteries of downstream genes, and are instituted by signal inputs to regulatory genes encoding transcription factors. Functional linkages between genes determine which signals affect which regulatory genes, in space and time, and which gene batteries will be involved. Thus both inter cis-regulatory networks and intra cis-regulatory systems are specified by arrays of genomic target site sequences. A model of an intergenic network of this kind that controls endomesoderm specification in sea urchin embryos has been constructed on the basis of experimental information. This model consists of a set of predicted inputs and outputs to a minimal group of regulatory genes encoding endodermal and mesodermal transcription factors, and components of signaling systems. The predictions of the model are experimentally testable, and indeed some such model is a clear necessity for productive experimental analysis.