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Phenotypic variation meets systems biology

DOI: 10.1186/gb-2009-10-8-313

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This year's annual growth factor and signal transduction symposium held at Iowa State University focused on systems-biology approaches to the study and modeling of complex biological processes. The topics discussed covered a wide spectrum of recent advances, including systems-level approaches to understanding transcriptional and posttranscriptional regulation and systems-level analysis and modeling of the responses of biological systems to perturbations. A few of the highlights of the meeting in these fields are reported here.Transcriptional regulation can be broadly defined as the process in which transcription factors interact with each other, with DNA, and with other biomolecules to regulate gene expression. This complex regulatory process is the subject of intensive study utilizing a variety of experimental and computational techniques. Opening the meeting, David Hume (Roslin Institute, University of Edinburgh, UK) described his recent results on gene regulation in macrophages related to the RIKEN genome Network Project and FNTOM 4 (Functional Annotation of Mammalian Genome). Hume and his collaborators analyzed transcriptional control of the human monocytic cell line THP-1 throughout a time course of growth, arrest and differentiation. Using the deepCAGE technique, they measured the dynamics of genome-wide usage of transcription start sites. This analysis was followed with comparative genomics approaches to predict active regulatory motifs throughout time and to predict the key transcription factors driving differentiation and uncover their time-dependent activation. Some of the predicted factors were subsequently confirmed by knockdowns using small interfering RNAs. Challenging the concept of 'master regulators', Hume argued that cellular states are constrained by complex networks that involve a substantial number of both positive and negative regulations.Transcriptional regulation was also the focus of Timothy Ravasi (University of California, San Diego, USA)


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