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See detailDynamic cumulative activity of transcription factors as a mechanism of quantitative gene regulation.
He, Feng UL; Buer, Jan; Zeng, An-Ping et al

in Genome Biology (2007), 8(9), 181

BACKGROUND: The regulation of genes in multicellular organisms is generally achieved through the combinatorial activity of different transcription factors. However, the quantitative mechanisms of how a ... [more ▼]

BACKGROUND: The regulation of genes in multicellular organisms is generally achieved through the combinatorial activity of different transcription factors. However, the quantitative mechanisms of how a combination of transcription factors controls the expression of their target genes remain unknown. RESULTS: By using the information on the yeast transcription network and high-resolution time-series data, the combinatorial expression profiles of regulators that best correlate with the expression of their target genes are identified. We demonstrate that a number of factors, particularly time-shifts among the different regulators as well as conversion efficiencies of transcription factor mRNAs into functional binding regulators, play a key role in the quantification of target gene expression. By quantifying and integrating these factors, we have found a highly significant correlation between the combinatorial time-series expression profile of regulators and their target gene expression in 67.1% of the 161 known yeast three-regulator motifs and in 32.9% of 544 two-regulator motifs. For network motifs involved in the cell cycle, these percentages are much higher. Furthermore, the results have been verified with a high consistency in a second independent set of time-series data. Additional support comes from the finding that a high percentage of motifs again show a significant correlation in time-series data from stress-response studies. CONCLUSION: Our data strongly support the concept that dynamic cumulative regulation is a major principle of quantitative transcriptional control. The proposed concept might also apply to other organisms and could be relevant for a wide range of biotechnological applications in which quantitative gene regulation plays a role. [less ▲]

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See detailMice, microbes and models of infection.
Buer, Jan; Balling, Rudi UL

in Nature Reviews. Genetics (2003), 4(3), 195-205

We urgently need animal models to study infectious disease. Mice are susceptible to a similar range of microbial infections as humans. Marked differences between inbred strains of mice in their response ... [more ▼]

We urgently need animal models to study infectious disease. Mice are susceptible to a similar range of microbial infections as humans. Marked differences between inbred strains of mice in their response to pathogen infection can be exploited to analyse the genetic basis of infections. In addition, the genetic tools that are available in the laboratory mouse, and new techniques to monitor the expression of bacterial genes in vivo, make it the principal experimental animal model for studying mechanisms of infection and immunity. [less ▲]

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