Uri Alon
Weizmann Institute, Rehovot
The recent advance in large scale monitoring
of gene expression raises the challenge of
'reverse-engineering' systems based on kinetic
expression data. To solve such an inverse
problem, mapping genetic circuits from input-output
measurements, requires new analysis and experimental
methods.
Here, we examine this using one of the best-characterized
gene regulation networks, the flagella system
of Escherichia coli. Classical genetics ordered
the 14 flagella operons into a three-class
hierarchy.
We measured promoter activity at high temporal
resolution using reporter plasmids. A temporal
clustering algorithm captures not only the
genetically defined hierarchy, but a much
more detailed temporal program of transcription
than was previously thought. The order of
activation follows multiple steps of flagella
basal body assembly, followed by flagella
filament genes, and culminates with the chemotaxis
'computer'. A mechanism for temporal programming
is proposed based on graded regulatory site
affinities.
Thus, detailed analysis of expression kinetics
might be a feasible high-throughput complement
to genetics in ordering gene regulation and
assembly cascades.