Nucleic Acids Research Advance Access published online on April 22, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm201
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Computational Biology |
Position and distance specificity are important determinants of cis-regulatory motifs in addition to evolutionary conservation
Penn Center for Bioinformatics, Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104-6021
*To whom correspondence should be addressed. Tel: +215 746 8683; Fax: +215 573 3111; Email: sridharh{at}pcbi.upenn.edu
Received December 5, 2006. Revised March 16, 2007. Accepted March 21, 2007.
Computational discovery of cis-regulatory elements remains challenging. To cope with the high false positives, evolutionary conservation is routinely used. However, conservation is only one of the attributes of cis-regulatory elements and is neither necessary nor sufficient. Here, we assess two additional attributes—positional and inter-motif distance specificity—that are critical for interactions between transcription factors. We first show that for a greater than expected fraction of known motifs, the genes that contain the motifs in their promoters in a position-specific or distance-specific manner are related, both in function and/or in expression pattern. We then use the position and distance specificity to discover novel motifs. Our work highlights the importance of distance and position specificity, in addition to the evolutionary conservation, in discovering cis-regulatory motifs.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Vandenbon and K. Nakai Modeling tissue-specific structural patterns in human and mouse promoters Nucleic Acids Res., January 1, 2010; 38(1): 17 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zeng, S. Zhu, and H. Yan Towards accurate human promoter recognition: a review of currently used sequence features and classification methods Brief Bioinform, September 1, 2009; 10(5): 498 - 508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. D. Yokoyama, U. Ohler, and G. A. Wray Measuring spatial preferences at fine-scale resolution identifies known and novel cis-regulatory element candidates and functional motif-pair relationships Nucleic Acids Res., July 1, 2009; 37(13): e92 - e92. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. N. Hutchins, S. M. Murphy, P. Singh, and J. H. Graber Position-dependent motif characterization using non-negative matrix factorization Bioinformatics, December 1, 2008; 24(23): 2684 - 2690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Friedman, M. B. Stadler, N. Shomron, Y. Ding, and C. B. Burge Ab initio identification of functionally interacting pairs of cis-regulatory elements Genome Res., October 1, 2008; 18(10): 1643 - 1651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hackenberg and R. Matthiesen Annotation-Modules: a tool for finding significant combinations of multisource annotations for gene lists Bioinformatics, June 1, 2008; 24(11): 1386 - 1393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tharakaraman, O. Bodenreider, D. Landsman, J. L. Spouge, and L. Marino-Ramirez The biological function of some human transcription factor binding motifs varies with position relative to the transcription start site Nucleic Acids Res., May 1, 2008; 36(8): 2777 - 2786. [Abstract] [Full Text] [PDF]
|
|