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


CONCLUSIONS
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.
Westholm
Jakub Orzechowski
JO
The Linnaeus Centre for Bioinformatics, Uppsala University, Uppsala, Sweden. jakub@lcb.uu.se
Xu
Feifei
F
Ronne
Hans
H
Komorowski
Jan
J
D020816:Amino Acid Motifs; D001665:Binding Sites; D004247:DNA / Q000737:chemistry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D008957:Models, Genetic; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA