Oral Presentation 31

Functional Regulatory Circuits Induced by Transcription Factors and Small RNAs

Presenter: Molly Megraw, Duke University
Authors: Molly Megraw, Uwe Ohler

Abstract: A program of tightly regulated gene expression is at the heart of development for every living organism. Recent years have seen an increased appreciation for the complexity of transcriptional control by gene Transcription Factors (TFs) as well as post-transcriptional control by small RNAs known as microRNAs (miRNAs). Several specific cases of small miRNA-TF regulatory circuits have been painstakingly discovered link by link using traditional genetic experiments. These examples all point to miRNA-TF circuits as crucial network components with important system-wide regulatory characteristics. They also highlight the need for systematic studies and methods to identify TF-miRNA circuits and query their biological function. The fundamental idea behind network motif discovery is that if a certain configuration (a 3-node cycle for example) is contained within a given network a surprisingly high number of times compared to many randomized networks, this configuration is likely to have been preserved through evolutionary time because it benefited the organism. However, motif identification is a useful concept only to the degree that the set of randomized background networks used for comparison are plausible as alternatives to the given network. Currently available background models were developed for use in TF-only networks and therefore have a number of shortcomings for use in TF-miRNA-gene networks. Here we present an algorithm that assigns edges in a manner that accounts for the unique biological constraints between each type of network entity, creating a more flexible and realistic background randomization model. We discuss network motifs identified in the Arabidopsis thaliana model plant system.

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