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Whitehead Team Creates Yeast Proteome/Genome Interaction Map

NEW YORK, Oct. 25--Researchers at the Whitehead Institute have built a genomic map of gene and protein interactions in Saccharomyces cerevisiae, creating a portrait of the  intricate nested networks of eukaryotic gene regulation.


The study, which appears in today's issue of the journal Science, was an effort to understand how gene expression is regulated in living cells.


A group led by the Massachusetts Institute of Technology's David Gifford and Whitehead's Tong Ihn Lee and Richard Young used a technique they call location analysis to figure out how each of the 141 known yeast transcription factors bind to gene promoter sequences.


Using microarrays, the team was able to label 106 of these proteins and observe nearly 4,000 regulator/promoter interactions involving 2,343 of the yeast's 6,270 genes. Interestingly, they found that in some cases, a single yeast promoter region was bound by many transcriptional regulators, a phenomenon previously thought to be limited to higher eukaryotes.


Compiling this data, Young's group constructed a complex model of interconnected regulatory networks in the cell. "The control of most, if not all, cellular processes is characterized by networks of transcriptional regulators that regulate other regulators," they write.


In the paper, the team proposes six different models of network "motifs" of transcription/promoter interaction, which in many cases describe elaborate feedback loops between promoters and regulators in the same functional category. They then assembled these into a framework to predict the entire regulatory process and gene expression patterns of the yeast cell cycle.


The team is currently working to apply the same technique to the roughly 1,7000 known transcription factors in human cells.

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