Human NRCAM DNA motifs Homology Phylogeny Motifs
MOTIF
Using the mRNA sequence for transcript variant 1 (isoform A), many motifs were identified using the MOTIF search and the list narrowed from 174 motifs at a default cutoff of 85, to 14 motifs at a cutoff value of 99. This higher cutoff score will more likely return DNA motifs that are more unique or more critical to the NRCAM gene.
The following is a list of motifs identified by Transfac in the MOTIF databse.
Motif Consensus Function
HSF (Drosophila) AGAAN heat shock factor
HSF (yeast) AGAAN heat shock factor
MATalpha2 NCRTGTNNWN mating factor alpha2
GCR1 RGCTTCCWC
ADR1 NGGRGK alcohol dehydrogenase gene regulator 1
CdxA MTTTATR
Lyf-1 TTTGGGAGR
NIT2 TATCTM activator of nitrogen-regulated genes
SRY AAACWAM sex-determining region Y gene product
Nkx-2.5 TYAAGTG homeo domain factor Nkx-2.5/Csx, tinman homolog
cap NCANNNNN cap signal for transcription initiation
AML-1a TGTGGT runt-factor AML-1
NF-AT NNNWGGAAAANM nuclear factor of activated T-cells
Cdxa WWTWMTR
MEME
The NRCAM transcript variant 1 (isoform A) sequence was used in the MEME analysis, and three motifs were returned by the algorithm [1]. These motifs are modeled in a logo format with the size and color of the base pairs indicating the certainty of that base pair at that position.
In analyzing the NRCAM sequence for DNA motifs, I used two different programs MOTIF and MEME. Of the two programs MEME returned motifs that were on average longer in size, but with much less information about the motif, including the name of the motif which seems to be critical in our analysis. I was disappointed with the limited feedback I got from the MEME searches, though the way they present the data is much nicer. The logo format is more optimal for visualizing the output as the size and color of the base pairs give you information about the motif that would otherwise be included in a key.
The results that the MOTIF search returned included DNA motifs that were between 6 and 15 base pairs--much smaller and MEME results--and also provided the name and a short description for many of the motifs. Adjusting the search parameters in MOTIF, especially the cutoff score, was very helpful in limiting the search results to motifs that may be specific to my gene of interest. I was able to narrow the list from 174 motifs at a cutoff score of 85 to 14 motifs at a cutoff score of 99. The format of the consensus output was not as nice in MOTIF using letters to represent multiple base pairs at a given location rather than the logo format used in MEME.
Surprisingly (or maybe not!) there does not seem to be any overlap between the DNA motifs returned by each program. Further analysis of the motifs will be done for the final project, but from the data returned by the searches, it is difficult to make any predictions about how these motifs influence the function of the gene in autism.
1. Bailey, T.L., and Elkan, C. (1994). Fitting a mixture model by expectation maximization to discover motifs in
biopolymers. Proceedings of the Second International Conference on Intelligent Systems for Molecular Biology,
pp. 28-36, AAAI Press, Menlo Park, California, 1994.
