Research article

Genome-scale study of the importance of binding site context for transcription factor binding and gene regulation

Jakub Orzechowski Westholm¹ , Feifei Xu¹ , Hans Ronne² and Jan Komorowski^1,3

¹The Linnaeus Centre for Bioinformatics, Uppsala University, BMC, Box 598, SE-751 24 Uppsala, Sweden

²Department of Medical Biochemistry and Microbiology, Uppsala University, BMC, Box 582, SE-751 23 Uppsala, Sweden

³Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University, 02-106, Warsaw, Poland

author email corresponding author email

BMC Bioinformatics 2008, 9:484doi:10.1186/1471-2105-9-484

Published:	17 November 2008

Abstract

Background

The rate of mRNA transcription is controlled by transcription factors that bind to specific DNA motifs in promoter regions upstream of protein coding genes. Recent results indicate that not only the presence of a motif but also motif context (for example the orientation of a motif or its location relative to the coding sequence) is important for gene regulation.

Results

In this study we present ContextFinder, a tool that is specifically aimed at identifying cases where motif context is likely to affect gene regulation. We used ContextFinder to examine the role of motif context in S. cerevisiae both for DNA binding by transcription factors and for effects on gene expression. For DNA binding we found significant patterns of motif location bias, whereas motif orientations did not seem to matter. Motif context appears to affect gene expression even more than it affects DNA binding, as biases in both motif location and orientation were more frequent in promoters of co-expressed genes. We validated our results against data on nucleosome positioning, and found a negative correlation between preferred motif locations and nucleosome occupancy.

Conclusion

We conclude that the requirement for stable binding of transcription factors to DNA and their subsequent function in gene regulation can impose constraints on motif context.