Abstract

A comprehensive understanding of the transcriptional regulation of embryonic stem cell (ESC) fate decisions will provide the key to their successful manipulation for therapeutic purposes as well as provide insight into the process of early embryogenesis. Traditional molecular and genetic approaches have been successful in identifying several essential regulators of pluripotency, notably Oct4, Nanog, and Sox2. However, these approaches will not be sufficient to understand the global regulatory control of transcriptional networks. Genome-wide work in model organisms such as Escherichia coli, yeast, and sea urchin reveal that transcriptional networks can be broken down into a small set of evolutionarily conserved network motifs, each with its own biological function. Initial genome-wide studies in ESCs reveal the presence of these same network motifs, providing mechanistic explanations of cell fate decisions. Thus, as is being performed in lower organisms, the drafting of a comprehensive transcriptional network controlling ESC fate will require systematic characterisation of the functional targets of each ESC-expressed transcription factor.

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