Published online 12 January 2005
Article |
Inferring combinatorial regulation of transcription in silico
basaHumboldt University, Institute for Theoretical Biology Invalidenstrasse 43, 10115 Berlin, Germany
*To whom correspondence should be addressed. Tel: +49 30 2093 9112; Fax: +49 30 2093 8801; Email: nils.bluethgen{at}itb.biologie.hu-berlin.de
Received September 5, 2004. Revised November 3, 2004. Accepted December 15, 2004.
In this paper, we propose a functional view on the in silico prediction of transcriptional regulation. We present a method to predict biological functions regulated by a combinatorial interaction of transcription factors. Using a rigorous statistic, this approach intersects the presence of transcription factor binding sites in gene upstream sequences with Gene Ontology terms associated with these genes. We demonstrate that for the well-studied set of skeletal muscle-related transcription factors Myf-2, Mef and TEF, the correct functions are predicted. Furthermore, starting from the well-characterized promoter of a gene expressed upon lipopolysaccharide stimulation, we predict functional targets of this stimulus. These results are in excellent agreement with microarray data.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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