TY - JOUR
T1 - Position and distance specificity are important determinants of cis-regulatory motifs in addition to evolutionary conservation
AU - Vardhanabhuti, Saran
AU - Wang, Junwen
AU - Hannenhalli, Sridhar
N1 - Funding Information:
This work and the Open Access publication charges were funded by NIH grant R21GM078203.
PY - 2007/5
Y1 - 2007/5
N2 - 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 distancespecific 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.
AB - 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 distancespecific 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.
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U2 - 10.1093/nar/gkm201
DO - 10.1093/nar/gkm201
M3 - Article
C2 - 17452354
AN - SCOPUS:34250896139
VL - 35
SP - 3203
EP - 3213
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 10
ER -