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Evolution and Dynamics of Transcriptional Regulatory Networks

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Evolution and dynamics of transcription factor repertoires

Sarah A. Teichmann, MRC Laboratory of Molecular Biology, Cambridge, UK.

Regulation of gene expression influences almost all biological processes in an organism, and sequence-specific DNA -binding transcription factors are critical to this control. These transcription factors are involved in complex circuits of regulation between transcription factors and target genes (Babu et al., 2004). Transcription factors that bind specific DNA sequences are arguably the core information-carrying molecules in regulatory networks, and are therefore of particular interest in understanding the evolution of organismal complexity.

However, for most genomes, the repertoire of transcription factors is only partially known. To fill this void, we have developed a novel transcription factor identification method, providing genome-wide transcription factor predictions for organisms from across the tree of life, available at www.transcriptionfactor.org (Kummerfeld & Teichmann, 2006).

By integrating annotated transcription factors with expression data, we have started to gain insight into the dynamics of transcription factor expression under different cellular conditions in a unicellular organism (Luscombe et al,. 2004) and in different developmental stages and tissues in a multi-cellular organism. Both analyses reveal the importance of combinatorial action of transcription factors to determine the state of a cell, and the role of ubiquitous transcription factor hubs.

We have investigated the evolution of transcription factors in both prokaryotes and eukaryotes. A general trend emerges across all different groups of organisms, showing that transcription factors, as well as other classes of regulatory molecules evolve more quickly than genes in other functional categories, such as enzymes for instance. This suggests that transcription factors are ‘evolvable’ in the sense that duplications and losses of transcription factors are tolerated more easily than for core functional classes. The changes in transcription factor repertoires are likely to play a large part in evolution of development and complexity.

References

Kummerfeld & Teichmann (2006) DBD : Kummerfeld, S.K. & Teichmann, S.A. (2006) DBD : a transcription factor prediction database. Nucleic Acids Res., 34, D74 -81.

Babu, M.M., Luscombe, N.M., Aravind, L., Gerstein, M. & Teichmann, S.A. (2004) Structure and evolution of transcriptional regulatory networks. Curr. Op. Struc. Biol., 14, 283-291

Luscombe, N.M., Babu, M.M., Yu, H., Snyder, M., Teichmann, S.A., Gerstein, M. (2004) Genomic analysis of regulatory network dynamics reveals large topological change. Nature, 431, 308-312.

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