Table 1. Summary of identification of putative HREs in genes regulating melanocyte and melanoma behavior.
| Gene | Accession Number | Number of HREs upstream of Start Site | Number of HREs after start site | Location after start site | Genes identified with a strong matrix score |
|---|---|---|---|---|---|
| POMC |
NM_000939 |
1 (-248) |
2 (209 and 383) |
First Intron |
|
| MC1R |
NM_002386 |
2 (-1372 and -1799) |
1 (143) |
First Exon |
|
| MITF |
NM_198159 |
3 (-198, -950 and -1699) |
0 |
- |
|
| SOX10 |
NM_006941 |
2 (-387 and -640) |
0 |
- |
|
| SOX5 (transcript variant 1) |
NM_006940 |
1 (-720) |
0 |
- |
|
| SOX5 (transcript variant 2) |
NM_152989 |
2 (-1218 and -1577) |
0 |
- |
|
| SOX9 |
NM_000346 |
0 |
0 |
- |
|
| SOX18 |
NM_018419 |
1 (-1240) |
0 |
- |
|
| EDNRB (transcript variant 1) |
NM_000115 |
1 (-1422) |
2 (28 and 220) |
First Exon |
|
| EDNRB (transcript variant 2) |
NM_003991 |
2 (-128 and -1007) |
0 |
- |
|
| TRPM1 |
NM_002420 |
3 (-1074, -1103 and -1265) |
0 |
- |
Strong Matrix Scores, p = 4.73E-05 |
| SLC45A2 |
NM_016180 |
7 (from -237 to -1326) |
0 |
- |
Strong Matrix Scores, p = 4.25E-10 |
| GPCR143 |
NM_000273 |
2 (-806 and -1661) |
2 (230 and 446) |
First Intron |
|
| BRAF |
NM_004333 |
0 |
0 |
- |
|
| HRAS |
NM_005343 |
4 (-36, -1322, -1684 and -1811) |
1 (472) |
First Intron |
Strong Matrix Scores, p = 4.32E-10 |
| INK4/p16 |
NM_000077 |
1 (-1216) |
1 (148) |
First Intron |
|
| c-Kit |
NM_000222 |
4 (-142, -404, -687 and -726) |
0 |
- |
Strong Matrix Scores, p = 1.93E-04 |
| TYR |
NM_000372 |
0 |
0 |
- |
|
| TYRP1 |
NM_000550 |
0 |
1 (126) |
First Exon |
|
| TYRP2 |
NM_001922 |
0 |
1 (231) |
First Exon |
|
| MLANA |
NM_005511 |
1 (-721) |
0 |
- |
|
| PMEL |
NM_006928 |
2 (-1011 and -1086) |
0 |
- |
Strong Matrix Scores, p = 4.32E-04 |
| VDR |
NM_000376 |
0 |
0 |
- |
|
| CYP27B1 |
NM_000785 |
0 |
1 (248) |
First Intron |
|
| CYP27A1 |
NM_000784 |
1 (-993) |
2 (346 and 400) |
First Intron |
|
| CRH |
NM_000756 |
0 |
3 (260, 280 and 338) |
First Exon |
Strong Matrix Scores, p = 3.81E-05 |
| CRHR1 |
NM_004382 |
0 |
0 |
- |
|
| CRHR2 |
NM_001883 |
1 (-476) |
0 |
- |
|
| UCN |
NM_003353 |
1 (-311) |
1 (161) |
First Exon |
|
| UCN2 |
NM_033199 |
4 (-524, -542, -1557 and -1875 |
0 |
- |
|
| UCN3 | NM_053049 | 1 (-20) | 1 (134) | First Exon |
The promoter regions of genes known to regulate melanocyte activity and melanoma were scanned for the presence of putative HIF response elements (HREs) using the publicly available web server, Transcription Factor Matrix (TFM) Explorer.156-158 A 2,500 base pair sequence (2,000 base pairs upstream of the start site and 500 base pairs after the start site) of each gene was scanned using weight matrices derived from JASPER and TRANSFAC® for the HRE sequence 5′-RCGTG-3′, where R is any purine (A or G.) Using this approach, a few genes were identified as having a significant matrix scores for the presence of an HRE (p < 0.001). The remaining genes were either not considered by these parameters to be significant for the presence of a consensus HRE site, or no HRE was identified in the scanned sequence submitted for analysis. A summary of all of the analyzed genes and the locations of the HREs identified in the database search are presented.