The promoter region
and the 5'UTR for specific sets of genes was used for MatchT to search the most
recent TRANSFAC® Professional 8.1 database (vertebrates)
(http://www.biobase.de/) for common
regulatory elements. We determined statistical over-representation of the
common motifs compared to "all" (~20,000) human promoter sequences (UCSC hg17;
CLOVER) (Matys et al.,
2003)
and additionally we used the promoter sequences of the "other" gene set as
background.
We found
a total of 152 common transcription factor binding sites in the promoter
regions of these 59 genes (3kb 5' of the transcription start site).
Furthermore, we found significant over-representation of the same set of common
transcription factor binding sites when sequences were compared against either
"all" human promoter sequences or against the "other" 200 protein synthesis
related genes. All these transcription factors are expressed in ALL cells
except HEN1, but only ELF-1 was expressed at a significantly different level in
ALL cells that were VCR-sensitive plus ASP-resistant versus
VCR-resistance plus ASP-sensitive
(P=0.014, t-test, R/S ratio =1.28).
| Motif ID | Motif | TF | Raw score | P-value from 'all' * | P-value from 'other' + | |
| M00069 | V$YY1_02 | YY1 | 6.39 | 0 | 0.01 | |
| M00341 | V$GABP_B | GABP | 1.41 | 0.001 | 0.044 | |
| M00971 | V$ETS_Q6 | Ets | 2.6 | 0.002 | 0.024 | |
| M00746 | V$ELF1_Q6 | ELF-1$ | 5.15 | 0.009 | 0.012 | |
| M00068 | V$HEN1_01 | HEN1 | 2.28 | 0.017 | 0.003 | |
| M00264 | V$STAF_02 | Staf | 3.59 | 0.023 | 0.017 |
* P-value
from over-representation compared to "all" ~20,000 human promoter sequences
+ P-value from over-representation compared to promoter sequences of "other" 96 protein synthesis genes
$ P-value <0.05 in the two VCR-ASP
discordant resistance phenotypes