Morten Krogh and Kasper Astrup Eriksen
A connection between co-expression and the strength
of transcription factor binding.
Abstract
Background:
An important factor in the cellular machinery is the
relation between the combination of transcription factors
binding upstream of a gene and the resulting expression
level of the gene. Unravelling the interactions and
interplay between different transcription factors is thus
very important. Here we attack this issue by first asking
what is most important in determining the influence of a
transcription factor on its downstream target: The
intrinsic binding characteristics of the DNA -
transcription factor complex or whether there are other
stronger transcription factors capable of binding in the
same upstream region. As an intrinsic measure of the DNA -
transcription factor binding we use the p-value of binding
reported in location experiments.
Results:
First we demonstrate that the p-value is indeed a
biological meaningful measure by showing that its logarithm
is almost linearly related to how often a gene and its
transcription factor are co-expressed in microarray
experiments. This connection is, as expected, strongest for
microarray experiments performed in media resembling the
medium where the location p-values were measured. Somewhat
surprisingly we find that the existence of stronger
transcription factors does not affect how often a gene and
its transcription factor are co-expressed in Saccharomyces
Cerevisiae.
Discussion:
Our results indicate that important aspects of the
transcriptional regulation are already captured by the
intrinsic properties of the DNA - transcription factor
complex. In fact we failed to detect any signs of internal
competition between transcription factors beyond what
already is encoded in the p-value obtained from location
experiments. Our results emphasize that the individual
transcription factors do not simply act in an on/off
fashion, but come with a weight. This weight is at least
partially given by the p-value of binding as measured in
location experiments.
LU TP 03-30
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