Upstream stimulatory factor gene transcriptions

Associate Editor(s)-in-Chief: Henry A. Hoff

"A major environmental stress encountered by humans is solar UV light, which can cause skin inflammation, the induction of pro-inflammatory cytokines and skin ageing, as well as skin cancer, including the highly aggressive and increasingly common malignant melanoma (Elwood, 1996; Armstrong et al., 1997; Park and Gilchrest, 1999). The serious adverse effect of UV light on the skin has meant that humans have evolved an effective defence mechanism. In response to low levels of UV irradiation epidermal melanocytes increase the production of the pigment melanin in specialized organelles termed melanosomes (Jimbow et al., 1991). The melanosomes are transferred into surrounding keratinocytes where they act to protect against UV-induced DNA damage."

"The Tyrosinase gene encodes the rate-limiting enzyme for the production of melanin and is absolutely required for pigmentation; the absence of a functional tyrosinase enzyme results in an albino phenotype. Although much of the tanning response comprises a post-translational activation of the melanosome, transcription of the Tyrosinase gene is UV responsive (Hara et al., 1994; Sturm et al., 1994; Imokawa et al., 1995, 1997; Ota et al., 1998). However, analysis of the Tyrosinase promoter (Bentley et al., 1994; Ganss et al., 1994) failed to reveal any classical UV or stress-response element. The human Tyrosinase promoter comprises an SP1 site and two E box motifs, one at the initiator, and a second, termed the M box (Lowings et al., 1992), located at –100 with respect to the transcription initiation site (Bentley et al., 1994). The E box motifs are essential for Tyrosinase promoter activity and are highly evolutionarily conserved. Numerous studies (Bentley et al., 1994; Ganss et al., 1994; Hemesath et al., 1994; Yasumoto et al., 1994; Yavuzer et al., 1995; Krylov et al., 1997) have demonstrated that the Tyrosinase initiator E box and M box elements are targets for the microphthalmia-associated basic helix–loop–helix-leucine zipper (bHLH-LZ) transcription factor Mitf (Hodgkinson et al., 1993; Hughes et al., 1993). In addition to its role in regulating pigmentation genes, [the microphthalmia-associated transcription factor] Mitf is also critically required for the development of the melanocyte (Steingrímsson et al., 1994; Opdecamp et al., 1997)."

The "UV response is mediated by the ubiquitous bHLH-LZ transcription factor [upstream stimulatory factor] Usf-1, which, like Mitf, binds the conserved E box elements in the Tyrosinase promoter. The ability of Usf-1 to activate transcription is regulated by a signal transduction pathway that culminates in phosphorylation and activation of Usf-1 by the p38 stress-activated kinase."

"Usf-1 and Usf-2 bind the Tyrosinase promoter in vivo."

"USF comprises a combination of related ubiquitous bHLH-LZ transcription factors encoded by the Usf-1 and Usf-2 genes (Gregor et al., 1990; Sirito et al., 1992, 1994). Usf-1 and Usf-2 can form either homo- or heterodimers (Sirito et al., 1992; Viollet et al., 1996), and both are present in melanocytes and melanoma cell lines [...]."

Upstream stimulating or stimulatory factors

The "expressions of [Homeobox transcript antisense intergenic RNA] HOTAIR and upstream stimulatory factor 1 (USF1) was up-regulated, but miR-148b-3p was down-regulated in glioma microvascular endothelial cells (GECs)."

"Upstream stimulating factor (USF) includes upstream stimulating factor 1 (USF1) and upstream stimulating factor 2 (USF2), which belongs to the basic helix-loop-helix leucine zipper family of transcription factors. As an important regulatory factor, USF has highly conserved bHLH-LZ domain and binds to consensus sequence (CANNTG) of E-box to further regulate the transcription process of different proteins (Wu et al., 2013; Lupp et al., 2014). USF1 was reported to regulate the expression of IL-10 in glioma related microglia: inhibition of USF1 expression resulted in the up-regulation of IL-10 expression (Zhang et al., 2007). In liver cancer HepG2 cells, USF1 resisted oxygen sugar deprivation induced apoptosis by regulating miR-132 (Wang et al., 2014)."

"The helix-loop-helix transcription factor USF (upstream stimulating factor) binds to a regulatory sequence of the human insulin gene enhancer."

"The regulation of insulin gene expression is dependent on sequences located upstream of the transcription start site (Clark and Docherty, 1992). Two important cis-acting elements, the insulin enhancer binding site 1 (IEBI) or NIR box and the IEB2 or FAR box, have been identified in the rat insulin I gene (Karlsson et al., 1987, 1989). Located at positions -104 (IEBI/NIR) and -233 (IEB2/FAR), these elements share an identical 8 bp sequence, GCCATCTG, which contains a consensus sequence, CANNTG, characteristic of E-box elements (Kingston, 1989). E boxes are present in enhancers from a variety of genes, including immunoglobulin and muscle-specific genes, where they interact with transcription factors containing a helix-loop-helix (HLH) dimerization domain (Murre et al., 1989)."

"The IEB1 box is highly conserved among insulin genes, and is thus likely to play an important role in controlling transcription. The IEB2 site is not well conserved; in the rat insulin 2 gene the equivalent sequence is GCCACCCAGGAG, and in the human insulin gene the homologous sequence, which has been previously designated the GC2 box (Boam et al., 1990a), is GCCACCGG."

"Confirmation that USF bound at the IEB2 site was obtained using an oligonucleotide containing the USF binding site from the adenovirus MLP."

"GCCATCTG, which contains a consensus sequence, CANNTG", + "GCCACCGG." which suggests GCCANN(G/T)G. Adding in a portion in the rat insulin 2 gene the equivalent sequence is GCCACCCA yields GCCANN(C/G/T)(A/G).

Consensus sequences

A likely general USF box consensus sequence may be 3'-GCC(A/T)NN(C/G/T)(A/G)-5'.

Human genes

Gene ID: 7391 is USF1 upstream transcription factor 1 (aka upstream stimulatory factor 1). "This gene encodes a member of the basic helix-loop-helix leucine zipper family, and can function as a cellular transcription factor. The encoded protein can activate transcription through pyrimidine-rich initiator (Inr) elements and E-box motifs. This gene has been linked to familial combined hyperlipidemia (FCHL). Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been defined on chromosome 21."

1. NP_009053.1 upstream stimulatory factor 1 isoform 1 (variant 1).
2. NP_996888.1 upstream stimulatory factor 1 isoform 2 (variant 2).
3. NP_001263302.1 upstream stimulatory factor 1 isoform 1 (variant 3).

Gene ID: 7392 is USF2 upstream transcription factor 2, c-fos interacting. "This gene encodes a member of the basic helix-loop-helix leucine zipper family of transcription factors. The encoded protein can activate transcription through pyrimidine-rich initiator (Inr) elements and E-box motifs and is involved in regulating multiple cellular processes."

1. NP_003358.1 upstream stimulatory factor 2 isoform 1.
2. NP_997174.1 upstream stimulatory factor 2 isoform 2.
3. NP_001308079.1 upstream stimulatory factor 2 isoform 3.
4. XP_024307452.1 upstream stimulatory factor 2 isoform X1.
5. XP_005259254.1 upstream stimulatory factor 2 isoform X2.
6. XP_024307453.1 upstream stimulatory factor 2 isoform X3.
7. XP_016882688.1 upstream stimulatory factor 2 isoform X4.
8. XP_011525562.1 upstream stimulatory factor 2 isoform X5.
9. XP_011525563.1 upstream stimulatory factor 2 isoform X6.

Gene ID: 205717 is USF3 upstream transcription factor family member 3. "This gene encodes a large protein that contains a helix-loop-helix domain and a polyglutamine region. A deletion in the polyglutamine region was associated with risk for thyroid carcinoma."

1. NP_001009899.3 basic helix-loop-helix domain-containing protein USF3 (variant 1).
2. NR_111981.1 RNA Sequence (non-coding, variant 2).
3. XP_024309159.1 basic helix-loop-helix domain-containing protein USF3 isoform X1.
4. XP_024309160.1 basic helix-loop-helix domain-containing protein USF3 isoform X2.
5. XP_016861360.1 basic helix-loop-helix domain-containing protein USF3 isoform X1.
6. XP_016861361.1 basic helix-loop-helix domain-containing protein USF3 isoform X2.
7. XP_005247265.2 basic helix-loop-helix domain-containing protein USF3 isoform X2.

Gene ID: 100151645 is USF1P1 upstream transcription factor 1 pseudogene 1.

Hypotheses

1. A1BG has no USF boxes in either promoter.

USF samplings

Using the two versions of the consensus sequence and "⌘F" to locate these sequences in the nucleotides for A1BG listed in A1BG gene transcriptions revealed two occurrences (GCCTGGGA) and (GCCTTCCG) on the ZNF497 side.

For the Basic programs testing consensus sequence GCC(A/T)NN(C/G/T)(A/G) (starting with SuccessablesUSF.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

1. Negative strand, negative direction: 11, GCCTGACG at 4329, GCCACCGA at 2529, GCCTCCGA at 2359, GCCACCGA at 2202, GCCTAGGG at 1814, GCCACCGA at 1767, GCCACTCG at 870, GCCTAGTG at 705, GCCACCGA at 658, GCCTAGTG at 432, GCCACCGA at 385.
2. Positive strand, negative direction: 13, GCCTGGGA at 4302, GCCAGACG at 4235, GCCAGGCA at 4104, GCCAGGTG at 3953, GCCTGTCA at 3202, GCCACCCA at 3135, GCCAGGCA at 2521, GCCAGGTG at 2079, GCCAAAGG at 1639, GCCTCCCG at 1508, GCCAGGCA at 950, GCCAGGCA at 650, GCCATATG at 41.
3. Negative strand, positive direction: 27, GCCTCCTG at 4408, GCCTTCCG at 4243, GCCTCAGA at 4195, GCCTGGGA at 3760, GCCACATG at 3707, GCCTGTGG at 3436, GCCAATGG at 2910, GCCTCTGG at 2883, GCCAAAGG at 2828, GCCAGGGA at 2576, GCCTCCCA at 2532, GCCTCCCA at 2396, GCCACCCA at 1853, GCCTTGGG at 1800, GCCTTTCA at 1601, GCCACCGG at 1546, GCCTTCCG at 1434, GCCTTCCG at 1334, GCCACCGG at 1294, GCCTCATG at 1238, GCCACACG at 986, GCCTGCCG at 909, GCCACACG at 886, GCCTGCCG at 809, GCCTTCCG at 678, GCCAGCGG at 331, GCCTGGGA at 288.
4. Positive strand, positive direction: 4, GCCAACGG at 3492, GCCTCGTG at 1207, GCCTGACG at 748, GCCACCCG at 404.
5. inverse complement, negative strand, negative direction: 0.
6. inverse complement, positive strand, negative direction: 29, TGGGAGGC at 4273, CAGGAGGC at 4142, TGGGAGGC at 3991, TGGTTGGC at 3947, TAAGAGGC at 3896, TGGGAGGC at 3716, CAGATGGC at 3629, TAAAAGGC at 3442, CATCAGGC at 3397, CAGGAGGC at 3221, TGGGAGGC at 3082, TAGATGGC at 2907, CAGGAGGC at 2693, TGGAAGGC at 2559, TGGCAGGC at 2390, CCGGAGGC at 2358, TGGGAGGC at 2223, TGGGAGGC at 2106, TGGGAGGC at 1964, TGGGAGGC at 1797, TAGGAGGC at 1311, CAGGAGGC at 1279, TGGGAGGC at 1020, CAGGAGGC at 988, CAGGAGGC at 854, TGGGAGGC at 688, TGGGAGGC at 552, TGCGAGGC at 451, TGGGAGGC at 415.
7. inverse complement, negative strand, positive direction: 22, CCTGAGGC at 4189, CAGCAGGC at 3695, CGGGAGGC at 3675, CAACAGGC at 3637, CATCTGGC at 3406, CCTCTGGC at 2984, CCTCTGGC at 2884, TGCAAGGC at 2694, CACCTGGC at 2570, CACCTGGC at 2434, TCTTAGGC at 2367, TCTCAGGC at 2116, TCTCTGGC at 1993, CGGCAGGC at 1906, CGAGAGGC at 1568, CGAGAGGC at 1484, CGAGAGGC at 1384, TACCTGGC at 1200, CGTGTGGC at 1023, CAGGTGGC at 198, TCACAGGC at 158, CCTCAGGC at 91.
8. inverse complement, positive strand, positive direction: 15, CGGAAGGC at 4243, CCGTTGGC at 3912, TCGGTGGC at 2562, CCAGAGGC at 1961, CAGGTGGC at 1845, TCGGTGGC at 1608, TCGGTGGC at 1545, CGGAAGGC at 1434, CGGAAGGC at 1334, TCGGTGGC at 1293, CGAAAGGC at 1098, CGGAAGGC at 678, CGTCTGGC at 441, TCCAAGGC at 307, TGGGTGGC at 74.

USF (4560-2846) UTRs

1. Negative strand, negative direction: GCCTGACG at 4329.
2. Positive strand, negative direction: GCCTGGGA at 4302, GCCAGACG at 4235, GCCAGGCA at 4104, GCCAGGTG at 3953, GCCTGTCA at 3202, GCCACCCA at 3135.
3. Positive strand, negative direction: TGGGAGGC at 4273, CAGGAGGC at 4142, TGGGAGGC at 3991, TGGTTGGC at 3947, TAAGAGGC at 3896, TGGGAGGC at 3716, CAGATGGC at 3629, TAAAAGGC at 3442, CATCAGGC at 3397, CAGGAGGC at 3221, TGGGAGGC at 3082, TAGATGGC at 2907.

USF positive direction (4445-4265) core promoters

1. Negative strand, positive direction: GCCTCCTG at 4408.

USF negative direction (2811-2596) proximal promoters

1. Positive strand, negative direction: CAGGAGGC at 2693.

USF positive direction (4265-4050) proximal promoters

1. Negative strand, positive direction: GCCTTCCG at 4243, GCCTCAGA at 4195.
2. Negative strand, positive direction: CCTGAGGC at 4189.

USF negative direction (2596-1) distal promoters

1. Negative strand, negative direction: GCCACCGA at 2529, GCCTCCGA at 2359, GCCACCGA at 2202, GCCTAGGG at 1814, GCCACCGA at 1767, GCCACTCG at 870, GCCTAGTG at 705, GCCACCGA at 658, GCCTAGTG at 432, GCCACCGA at 385.
2. Positive strand, negative direction: GCCAGGCA at 2521, GCCAGGTG at 2079, GCCAAAGG at 1639, GCCTCCCG at 1508, GCCAGGCA at 950, GCCAGGCA at 650, GCCATATG at 41.
3. Positive strand, negative direction: TGGAAGGC at 2559, TGGCAGGC at 2390, CCGGAGGC at 2358, TGGGAGGC at 2223, TGGGAGGC at 2106, TGGGAGGC at 1964, TGGGAGGC at 1797, TAGGAGGC at 1311, CAGGAGGC at 1279, TGGGAGGC at 1020, CAGGAGGC at 988, CAGGAGGC at 854, TGGGAGGC at 688, TGGGAGGC at 552, TGCGAGGC at 451, TGGGAGGC at 415.

USF positive direction (4050-1) distal promoters

1. Negative strand, positive direction: GCCTGGGA at 3760, GCCACATG at 3707, GCCTGTGG at 3436, GCCAATGG at 2910, GCCTCTGG at 2883, GCCAAAGG at 2828, GCCAGGGA at 2576, GCCTCCCA at 2532, GCCTCCCA at 2396, GCCACCCA at 1853, GCCTTGGG at 1800, GCCTTTCA at 1601, GCCACCGG at 1546, GCCTTCCG at 1434, GCCTTCCG at 1334, GCCACCGG at 1294, GCCTCATG at 1238, GCCACACG at 986, GCCTGCCG at 909, GCCACACG at 886, GCCTGCCG at 809, GCCTTCCG at 678, GCCAGCGG at 331, GCCTGGGA at 288.
2. Negative strand, positive direction: CAGCAGGC at 3695, CGGGAGGC at 3675, CAACAGGC at 3637, CATCTGGC at 3406, CCTCTGGC at 2984, CCTCTGGC at 2884, TGCAAGGC at 2694, CACCTGGC at 2570, CACCTGGC at 2434, TCTTAGGC at 2367, TCTCAGGC at 2116, TCTCTGGC at 1993, CGGCAGGC at 1906, CGAGAGGC at 1568, CGAGAGGC at 1484, CGAGAGGC at 1384, TACCTGGC at 1200, CGTGTGGC at 1023, CAGGTGGC at 198, TCACAGGC at 158, CCTCAGGC at 91.
3. Positive strand, positive direction: GCCAACGG at 3492, GCCTCGTG at 1207, GCCTGACG at 748, GCCACCCG at 404.
4. Positive strand, positive direction: CCGTTGGC at 3912, TCGGTGGC at 2562, CCAGAGGC at 1961, CAGGTGGC at 1845, TCGGTGGC at 1608, TCGGTGGC at 1545, CGGAAGGC at 1434, CGGAAGGC at 1334, TCGGTGGC at 1293, CGAAAGGC at 1098, CGGAAGGC at 678, CGTCTGGC at 441, TCCAAGGC at 307, TGGGTGGC at 74.

USF random dataset samplings

1. USFr0: 8, GCCATACA at 3305, GCCATTTA at 2391, GCCTTATA at 2371, GCCTGGGG at 2318, GCCACCTA at 1885, GCCAAGGA at 917, GCCAAGGG at 330, GCCAGGGG at 670.
2. USFr1: 17, GCCTCCGA at 3926, GCCAGTCA at 3854, GCCAAGCG at 3395, GCCTAACA at 3311, GCCTTACA at 2886, GCCAATTA at 2601, GCCTTCCA at 2094, GCCTTGGG at 2007, GCCTTACG at 1695, GCCATCCG at 1678, GCCTTGCG at 1119, GCCTAATG at 1046, GCCACTGG at 919, GCCAAGGG at 845, GCCAGGGG at 669, GCCTTACG at 633, GCCTGATG at 451.
3. USFr2: 10, GCCAGCTG at 4212, GCCTTTCG at 4169, GCCAAGGG at 3901, GCCTTGCA at 3783, GCCTATTG at 3591, GCCAGGGG at 2281, GCCATTCG at 1473, GCCTCTTG at 1258, GCCTGCGA at 1233, GCCTTACA at 507.
4. USFr3: 10, GCCACGTA at 4081, GCCTCTCG at 3381, GCCAAGTG at 3239, GCCTCGTG at 3114, GCCTGCTG at 2713, GCCTCTTA at 1871, GCCATCTG at 1770, GCCACCCG at 1394, GCCACCCG at 757, GCCACGCG at 587.
5. USFr4: 21, GCCTCCGA at 3766, GCCATGCA at 3660, GCCATTGG at 3576, GCCTTGGG at 3546, GCCTAGGA at 3167, GCCATTTA at 3027, GCCTATTA at 2933, GCCACTGG at 2686, GCCTTTGA at 2537, GCCATGTG at 2224, GCCAAGCG at 2217, GCCAATCA at 2109, GCCATGGA at 2052, GCCTGTCG at 2027, GCCTAGGG at 1989, GCCAAATG at 1363, GCCACGGG at 1285, GCCTGGTA at 1204, GCCATAGA at 1097, GCCTTTCG at 1082, GCCAATGA at 719.
6. USFr5: 16, GCCACTGA at 3915, GCCTCTGA at 3795, GCCAGCGA at 3639, GCCAACCA at 3080, GCCATTGA at 2805, GCCTAGTG at 2423, GCCAATTG at 2227, GCCAAGGA at 1998, GCCTACTA at 1803, GCCTTTTA at 1794, GCCAACTA at 1765, GCCTCATA at 1653, GCCATTTG at 1204, GCCAGCGG at 684, GCCTCGTA at 588, GCCACGCA at 74.
7. USFr6: 15, GCCTATTG at 4281, GCCAGCCG at 3405, GCCAAACA at 3206, GCCAATTG at 2488, GCCTGCGA at 2086, GCCTTTGA at 1711, GCCTCCGG at 1155, GCCTTTCA at 763, GCCAATGG at 742, GCCTCCGA at 556, GCCATCGG at 462, GCCTCGCA at 347, GCCAGGCG at 85, GCCAAGGG at 57, GCCTTGCA at 17.
8. USFr7: 14, GCCTTATG at 3988, GCCAACCA at 3689, GCCTGGCG at 3516, GCCTTGGA at 3365, GCCACTTG at 3118, GCCTATGG at 2716, GCCATTTG at 2446, GCCAAGCA at 2304, GCCTGTTA at 2198, GCCTGCCA at 2146, GCCTGCTG at 1762, GCCTTAGA at 1547, GCCAACCA at 485, GCCAAACA at 426.
9. USFr8: 15, GCCAGACG at 4406, GCCATTGG at 4023, GCCTACGA at 3113, GCCTTTTG at 3061, GCCACGGA at 2936, GCCAGCCA at 2789, GCCTCCGG at 2488, GCCATTGA at 2463, GCCTTTTG at 2254, GCCTTTGA at 1665, GCCAATGG at 1453, GCCTCGTG at 1212, GCCAATGA at 1131, GCCTAATA at 719, GCCAACGG at 130.
10. USFr9: 11, GCCTATGA at 3744, GCCTGTCA at 3573, GCCTGCTA at 2814, GCCTCCGA at 2766, GCCTGAGA at 2325, GCCTGGCG at 2006, GCCTAGCA at 1183, GCCTCCGG at 1039, GCCTAGCG at 994, GCCTACTA at 985, GCCATCGG at 366.
11. USFr0ci: 17, CCGGTGGC at 4263, TAACAGGC at 3997, TCCTAGGC at 3715, TCTGTGGC at 3671, CCCCTGGC at 3642, CGGGTGGC at 3424, CAGTAGGC at 3290, CCGCAGGC at 3245, CGCCAGGC at 2838, TCCCTGGC at 2436, CGCTAGGC at 2124, TATGTGGC at 2065, TGTCAGGC at 2030, TCTTTGGC at 1347, CGTCAGGC at 787, CAGCAGGC at 582, TAACTGGC at 138.
12. USFr1ci: 8, TCCTTGGC at 4085, TACAAGGC at 3574, CCTAAGGC at 2543, CATATGGC at 2103, TCGTAGGC at 2016, TGGAAGGC at 692, CCACAGGC at 445, TATTAGGC at 144.
13. USFr2ci: 19, TGGGTGGC at 4392, CGATAGGC at 4345, TCACTGGC at 4283, CACAAGGC at 4092, TAAGTGGC at 3681, CAAGAGGC at 3606, TATTAGGC at 3522, CCAAAGGC at 3263, CATAAGGC at 3255, TCACTGGC at 1728, TACCAGGC at 1221, CCATAGGC at 975, CATAAGGC at 870, CCGGTGGC at 817, TCCATGGC at 772, CCGTTGGC at 613, CCTGTGGC at 460, CAAATGGC at 429, CAAAAGGC at 111.
14. USFr3ci: 12, TGGTTGGC at 4109, TAGCTGGC at 3496, CCAATGGC at 3370, CCCAAGGC at 3108, TCAATGGC at 2694, CCATTGGC at 2354, CAGCAGGC at 2343, TCCAAGGC at 1907, TCGTTGGC at 1517, CAAGAGGC at 902, CCTGAGGC at 380, TAGCAGGC at 228.
15. USFr4ci: 13, CAAGAGGC at 4400, CGGTTGGC at 4247, CAGATGGC at 4204, CCCCTGGC at 3232, TATGTGGC at 2983, TCGCAGGC at 2804, TGGATGGC at 1904, CCCCTGGC at 1482, CGTGTGGC at 1457, CAAATGGC at 1365, TAATTGGC at 709, TGGTAGGC at 688, CCCATGGC at 637.
16. RDr5ci: TAGCTGGC at 4435, TCCTTGGC at 4422, TATAAGGC at 3586, TCGATGGC at 3062, CATTTGGC at 2792, TCTTTGGC at 2530, TGGAAGGC at 2392, CCGCAGGC at 2363, TGGAAGGC at 2346, CCAGAGGC at 1597, TACCTGGC at 1232, CGTCAGGC at 1028, CCCGTGGC at 732, CCCTTGGC at 355.
17. USFr6ci: 13, CAACAGGC at 4045, CACCAGGC at 3912, TCGTAGGC at 3722, TCAGTGGC at 3134, TGGGTGGC at 2157, CGAGTGGC at 2091, CCAATGGC at 1958, TACATGGC at 1894, CGGCAGGC at 1565, TCCCAGGC at 1400, CCCCAGGC at 685, TGAATGGC at 251, TGCCAGGC at 84.
18. USFr7ci: 10, TAGTAGGC at 4425, CATTTGGC at 4383, CGGCTGGC at 4019, CGCGAGGC at 3698, CGCCTGGC at 3515, TGGTAGGC at 3508, CCAATGGC at 3389, CCTAAGGC at 1710, TCGGTGGC at 1495, TGATAGGC at 1042.
19. USFr8ci: 13, CGTGAGGC at 4132, CCCGTGGC at 4088, CCCATGGC at 3257, CGATTGGC at 3240, CCAATGGC at 2423, TCCCTGGC at 2354, TATTTGGC at 2334, CCCGAGGC at 2282, TCGAAGGC at 1883, CCTATGGC at 1781, TCTGTGGC at 1715, TCAAAGGC at 937, CAGTAGGC at 258.
20. USFr9ci: 20, TGAATGGC at 4343, CCGGTGGC at 4047, CGAGAGGC at 3979, CCAAAGGC at 3930, TCCCTGGC at 3001, CCCGTGGC at 2944, TAATTGGC at 2852, TCAGAGGC at 2587, CGAGAGGC at 2305, TCCCAGGC at 2132, TCCTTGGC at 1893, TCAATGGC at 1724, CAAAAGGC at 1411, TAACAGGC at 1254, TAAGAGGC at 763, CGCAAGGC at 640, CCACTGGC at 487, CCCAAGGC at 340, TACAAGGC at 211, CCAGAGGC at 187.

USFr arbitrary (evens) (4560-2846) UTRs

1. USFr0: GCCATACA at 3305.
2. USFr2: GCCAGCTG at 4212, GCCTTTCG at 4169, GCCAAGGG at 3901, GCCTTGCA at 3783, GCCTATTG at 3591.
3. USFr4: GCCTCCGA at 3766, GCCATGCA at 3660, GCCATTGG at 3576, GCCTTGGG at 3546, GCCTAGGA at 3167, GCCATTTA at 3027, GCCTATTA at 2933.
4. USFr6: GCCTATTG at 4281, GCCAGCCG at 3405, GCCAAACA at 3206.
5. USFr8: GCCAGACG at 4406, GCCATTGG at 4023, GCCTACGA at 3113, GCCTTTTG at 3061, GCCACGGA at 2936.
6. USFr0ci: CCGGTGGC at 4263, TAACAGGC at 3997, TCCTAGGC at 3715, TCTGTGGC at 3671, CCCCTGGC at 3642, CGGGTGGC at 3424, CAGTAGGC at 3290, CCGCAGGC at 3245.
7. USFr2ci: TGGGTGGC at 4392, CGATAGGC at 4345, TCACTGGC at 4283, CACAAGGC at 4092, TAAGTGGC at 3681, CAAGAGGC at 3606, TATTAGGC at 3522, CCAAAGGC at 3263, CATAAGGC at 3255.
8. USFr4ci: CAAGAGGC at 4400, CGGTTGGC at 4247, CAGATGGC at 4204, CCCCTGGC at 3232, TATGTGGC at 2983.
9. USFr6ci: CAACAGGC at 4045, CACCAGGC at 3912, TCGTAGGC at 3722, TCAGTGGC at 3134.
10. USFr8ci: CGTGAGGC at 4132, CCCGTGGC at 4088, CCCATGGC at 3257, CGATTGGC at 3240.

USFr alternate (odds) (4560-2846) UTRs

1. USFr1: GCCTCCGA at 3926, GCCAGTCA at 3854, GCCAAGCG at 3395, GCCTAACA at 3311, GCCTTACA at 2886.
2. USFr3: GCCACGTA at 4081, GCCTCTCG at 3381, GCCAAGTG at 3239, GCCTCGTG at 3114.
3. USFr5: GCCACTGA at 3915, GCCTCTGA at 3795, GCCAGCGA at 3639, GCCAACCA at 3080.
4. USFr7: GCCTTATG at 3988, GCCAACCA at 3689, GCCTGGCG at 3516, GCCTTGGA at 3365, GCCACTTG at 3118.
5. USFr9: GCCTATGA at 3744, GCCTGTCA at 3573.
6. USFr1ci: TCCTTGGC at 4085, TACAAGGC at 3574.
7. USFr3ci: TGGTTGGC at 4109, TAGCTGGC at 3496, CCAATGGC at 3370, CCCAAGGC at 3108.
8. USFr5ci: TAGCTGGC at 4435, TCCTTGGC at 4422, TATAAGGC at 3586, TCGATGGC at 3062.
9. USFr7ci: TAGTAGGC at 4425, CATTTGGC at 4383, CGGCTGGC at 4019, CGCGAGGC at 3698, CGCCTGGC at 3515, TGGTAGGC at 3508, CCAATGGC at 3389.
10. USFr9ci: TGAATGGC at 4343, CCGGTGGC at 4047, CGAGAGGC at 3979, CCAAAGGC at 3930, TCCCTGGC at 3001, CCCGTGGC at 2944, TAATTGGC at 2852.

USFr arbitrary negative direction (evens) (2846-2811) core promoters

1. USFr0ci: CGCCAGGC at 2838.

USFr alternate negative direction (odds) (2846-2811) core promoters

1. USFr9: GCCTGCTA at 2814.

USFr arbitrary positive direction (odds) (4445-4265) core promoters

1. USFr5ci: TAGCTGGC at 4435, TCCTTGGC at 4422.
2. USFr7ci: TAGTAGGC at 4425, CATTTGGC at 4383.
3. USFr9ci: TGAATGGC at 4343.

USFr alternate positive direction (evens) (4445-4265) core promoters

1. USFr6: GCCTATTG at 4281.
2. USFr8: GCCAGACG at 4406.
3. USFr2ci: TGGGTGGC at 4392, CGATAGGC at 4345, TCACTGGC at 4283.
4. USFr4ci: CAAGAGGC at 4400.

USFr arbitrary negative direction (evens) (2811-2596) proximal promoters

1. USFr4: GCCACTGG at 2686.
2. USFr8: GCCAGCCA at 2789.
3. USFr4ci: TCGCAGGC at 2804.

USFr alternate negative direction (odds) (2811-2596) proximal promoters

1. USFr1: GCCAATTA at 2601.
2. USFr3: GCCTGCTG at 2713.
3. USFr5: GCCATTGA at 2805.
4. USFr7: GCCTATGG at 2716.
5. USFr9: GCCTCCGA at 2766.
6. USFr3ci: TCAATGGC at 2694.
7. USFr5ci: CATTTGGC at 2792.

USFr arbitrary positive direction (odds) (4265-4050) proximal promoters

1. USFr3: GCCACGTA at 4081.
2. USFr1ci: TCCTTGGC at 4085.
3. USFr3ci: TGGTTGGC at 4109.

USFr alternate positive direction (evens) (4265-4050) proximal promoters

1. USFr2: GCCAGCTG at 4212, GCCTTTCG at 4169.
2. USFr0ci: CCGGTGGC at 4263.
3. USFr2ci: CACAAGGC at 4092.
4. USFr4ci: CGGTTGGC at 4247, CAGATGGC at 4204.
5. USFr8ci: CGTGAGGC at 4132, CCCGTGGC at 4088.

USFr arbitrary negative direction (evens) (2596-1) distal promoters

1. USFr0: GCCATTTA at 2391, GCCTTATA at 2371, GCCTGGGG at 2318, GCCACCTA at 1885, GCCAAGGA at 917, GCCAAGGG at 330, GCCAGGGG at 670.
2. USFr2: GCCAGGGG at 2281, GCCATTCG at 1473, GCCTCTTG at 1258, GCCTGCGA at 1233, GCCTTACA at 507.
3. USFr4: GCCTTTGA at 2537, GCCATGTG at 2224, GCCAAGCG at 2217, GCCAATCA at 2109, GCCATGGA at 2052, GCCTGTCG at 2027, GCCTAGGG at 1989, GCCAAATG at 1363, GCCACGGG at 1285, GCCTGGTA at 1204, GCCATAGA at 1097, GCCTTTCG at 1082, GCCAATGA at 719.
4. USFr6: GCCAATTG at 2488, GCCTGCGA at 2086, GCCTTTGA at 1711, GCCTCCGG at 1155, GCCTTTCA at 763, GCCAATGG at 742, GCCTCCGA at 556, GCCATCGG at 462, GCCTCGCA at 347, GCCAGGCG at 85, GCCAAGGG at 57, GCCTTGCA at 17.
5. USFr8: GCCTCCGG at 2488, GCCATTGA at 2463, GCCTTTTG at 2254, GCCTTTGA at 1665, GCCAATGG at 1453, GCCTCGTG at 1212, GCCAATGA at 1131, GCCTAATA at 719, GCCAACGG at 130.
6. USFr0ci: TCCCTGGC at 2436, CGCTAGGC at 2124, TATGTGGC at 2065, TGTCAGGC at 2030, TCTTTGGC at 1347, CGTCAGGC at 787, CAGCAGGC at 582, TAACTGGC at 138.
7. USFr2ci: TCACTGGC at 1728, TACCAGGC at 1221, CCATAGGC at 975, CATAAGGC at 870, CCGGTGGC at 817, TCCATGGC at 772, CCGTTGGC at 613, CCTGTGGC at 460, CAAATGGC at 429, CAAAAGGC at 111.
8. USFr4ci: TGGATGGC at 1904, CCCCTGGC at 1482, CGTGTGGC at 1457, CAAATGGC at 1365, TAATTGGC at 709, TGGTAGGC at 688, CCCATGGC at 637.
9. USFr6ci: TGGGTGGC at 2157, CGAGTGGC at 2091, CCAATGGC at 1958, TACATGGC at 1894, CGGCAGGC at 1565, TCCCAGGC at 1400, CCCCAGGC at 685, TGAATGGC at 251, TGCCAGGC at 84.
10. USFr8ci: CCAATGGC at 2423, TCCCTGGC at 2354, TATTTGGC at 2334, CCCGAGGC at 2282, TCGAAGGC at 1883, CCTATGGC at 1781, TCTGTGGC at 1715, TCAAAGGC at 937, CAGTAGGC at 258.

USFr alternate negative direction (odds) (2596-1) distal promoters

1. USFr1: GCCTTCCA at 2094, GCCTTGGG at 2007, GCCTTACG at 1695, GCCATCCG at 1678, GCCTTGCG at 1119, GCCTAATG at 1046, GCCACTGG at 919, GCCAAGGG at 845, GCCAGGGG at 669, GCCTTACG at 633, GCCTGATG at 451.
2. USFr3: GCCTCTTA at 1871, GCCATCTG at 1770, GCCACCCG at 1394, GCCACCCG at 757, GCCACGCG at 587.
3. USFr5: GCCTAGTG at 2423, GCCAATTG at 2227, GCCAAGGA at 1998, GCCTACTA at 1803, GCCTTTTA at 1794, GCCAACTA at 1765, GCCTCATA at 1653, GCCATTTG at 1204, GCCAGCGG at 684, GCCTCGTA at 588, GCCACGCA at 74.
4. USFr7: GCCATTTG at 2446, GCCAAGCA at 2304, GCCTGTTA at 2198, GCCTGCCA at 2146, GCCTGCTG at 1762, GCCTTAGA at 1547, GCCAACCA at 485, GCCAAACA at 426.
5. USFr9: GCCTGAGA at 2325, GCCTGGCG at 2006, GCCTAGCA at 1183, GCCTCCGG at 1039, GCCTAGCG at 994, GCCTACTA at 985, GCCATCGG at 366.
6. USFr1ci: CCTAAGGC at 2543, CATATGGC at 2103, TCGTAGGC at 2016, TGGAAGGC at 692, CCACAGGC at 445, TATTAGGC at 144.
7. USFr3ci: CCATTGGC at 2354, CAGCAGGC at 2343, TCCAAGGC at 1907, TCGTTGGC at 1517, CAAGAGGC at 902, CCTGAGGC at 380, TAGCAGGC at 228.
8. USFr5ci: TCTTTGGC at 2530, TGGAAGGC at 2392, CCGCAGGC at 2363, TGGAAGGC at 2346, CCAGAGGC at 1597, TACCTGGC at 1232, CGTCAGGC at 1028, CCCGTGGC at 732, CCCTTGGC at 355.
9. USFr7ci: CCTAAGGC at 1710, TCGGTGGC at 1495, TGATAGGC at 1042.
10. USFr9ci: TCAGAGGC at 2587, CGAGAGGC at 2305, TCCCAGGC at 2132, TCCTTGGC at 1893, TCAATGGC at 1724, CAAAAGGC at 1411, TAACAGGC at 1254, TAAGAGGC at 763, CGCAAGGC at 640, CCACTGGC at 487, CCCAAGGC at 340, TACAAGGC at 211, CCAGAGGC at 187.

USFr arbitrary positive direction (odds) (4050-1) distal promoters

1. USFr1: GCCTCCGA at 3926, GCCAGTCA at 3854, GCCAAGCG at 3395, GCCTAACA at 3311, GCCTTACA at 2886, GCCAATTA at 2601, GCCTTCCA at 2094, GCCTTGGG at 2007, GCCTTACG at 1695, GCCATCCG at 1678, GCCTTGCG at 1119, GCCTAATG at 1046, GCCACTGG at 919, GCCAAGGG at 845, GCCAGGGG at 669, GCCTTACG at 633, GCCTGATG at 451.
2. USFr3: GCCTCTCG at 3381, GCCAAGTG at 3239, GCCTCGTG at 3114, GCCTGCTG at 2713, GCCTCTTA at 1871, GCCATCTG at 1770, GCCACCCG at 1394, GCCACCCG at 757, GCCACGCG at 587.
3. USFr5: GCCACTGA at 3915, GCCTCTGA at 3795, GCCAGCGA at 3639, GCCAACCA at 3080, GCCATTGA at 2805, GCCTAGTG at 2423, GCCAATTG at 2227, GCCAAGGA at 1998, GCCTACTA at 1803, GCCTTTTA at 1794, GCCAACTA at 1765, GCCTCATA at 1653, GCCATTTG at 1204, GCCAGCGG at 684, GCCTCGTA at 588, GCCACGCA at 74.
4. USFr7: GCCTTATG at 3988, GCCAACCA at 3689, GCCTGGCG at 3516, GCCTTGGA at 3365, GCCACTTG at 3118, GCCTATGG at 2716, GCCATTTG at 2446, GCCAAGCA at 2304, GCCTGTTA at 2198, GCCTGCCA at 2146, GCCTGCTG at 1762, GCCTTAGA at 1547, GCCAACCA at 485, GCCAAACA at 426.
5. USFr9: GCCTATGA at 3744, GCCTGTCA at 3573, GCCTGCTA at 2814, GCCTCCGA at 2766, GCCTGAGA at 2325, GCCTGGCG at 2006, GCCTAGCA at 1183, GCCTCCGG at 1039, GCCTAGCG at 994, GCCTACTA at 985, GCCATCGG at 366.
6. USFr1ci: TACAAGGC at 3574, CCTAAGGC at 2543, CATATGGC at 2103, TCGTAGGC at 2016, TGGAAGGC at 692, CCACAGGC at 445, TATTAGGC at 144.
7. USFr3ci: TAGCTGGC at 3496, CCAATGGC at 3370, CCCAAGGC at 3108, TCAATGGC at 2694, CCATTGGC at 2354, CAGCAGGC at 2343, TCCAAGGC at 1907, TCGTTGGC at 1517, CAAGAGGC at 902, CCTGAGGC at 380, TAGCAGGC at 228.
8. USFr5ci: TATAAGGC at 3586, TCGATGGC at 3062, CATTTGGC at 2792, TCTTTGGC at 2530, TGGAAGGC at 2392, CCGCAGGC at 2363, TGGAAGGC at 2346, CCAGAGGC at 1597, TACCTGGC at 1232, CGTCAGGC at 1028, CCCGTGGC at 732, CCCTTGGC at 355.
9. USFr7ci: CGGCTGGC at 4019, CGCGAGGC at 3698, CGCCTGGC at 3515, TGGTAGGC at 3508, CCAATGGC at 3389, CCTAAGGC at 1710, TCGGTGGC at 1495, TGATAGGC at 1042.
10. USFr9ci: CCGGTGGC at 4047, CGAGAGGC at 3979, CCAAAGGC at 3930, TCCCTGGC at 3001, CCCGTGGC at 2944, TAATTGGC at 2852, TCAGAGGC at 2587, CGAGAGGC at 2305, TCCCAGGC at 2132, TCCTTGGC at 1893, TCAATGGC at 1724, CAAAAGGC at 1411, TAACAGGC at 1254, TAAGAGGC at 763, CGCAAGGC at 640, CCACTGGC at 487, CCCAAGGC at 340, TACAAGGC at 211, CCAGAGGC at 187.

USFr alternate positive direction (evens) (4050-1) distal promoters

1. USFr0: GCCATACA at 3305, GCCATTTA at 2391, GCCTTATA at 2371, GCCTGGGG at 2318, GCCACCTA at 1885, GCCAAGGA at 917, GCCAAGGG at 330, GCCAGGGG at 670.
2. USFr2: GCCAAGGG at 3901, GCCTTGCA at 3783, GCCTATTG at 3591, GCCAGGGG at 2281, GCCATTCG at 1473, GCCTCTTG at 1258, GCCTGCGA at 1233, GCCTTACA at 507.
3. USFr4: GCCTCCGA at 3766, GCCATGCA at 3660, GCCATTGG at 3576, GCCTTGGG at 3546, GCCTAGGA at 3167, GCCATTTA at 3027, GCCTATTA at 2933, GCCACTGG at 2686, GCCTTTGA at 2537, GCCATGTG at 2224, GCCAAGCG at 2217, GCCAATCA at 2109, GCCATGGA at 2052, GCCTGTCG at 2027, GCCTAGGG at 1989, GCCAAATG at 1363, GCCACGGG at 1285, GCCTGGTA at 1204, GCCATAGA at 1097, GCCTTTCG at 1082, GCCAATGA at 719.
4. USFr6: GCCAGCCG at 3405, GCCAAACA at 3206, GCCAATTG at 2488, GCCTGCGA at 2086, GCCTTTGA at 1711, GCCTCCGG at 1155, GCCTTTCA at 763, GCCAATGG at 742, GCCTCCGA at 556, GCCATCGG at 462, GCCTCGCA at 347, GCCAGGCG at 85, GCCAAGGG at 57, GCCTTGCA at 17.
5. USFr8: GCCATTGG at 4023, GCCTACGA at 3113, GCCTTTTG at 3061, GCCACGGA at 2936, GCCAGCCA at 2789, GCCTCCGG at 2488, GCCATTGA at 2463, GCCTTTTG at 2254, GCCTTTGA at 1665, GCCAATGG at 1453, GCCTCGTG at 1212, GCCAATGA at 1131, GCCTAATA at 719, GCCAACGG at 130.
6. USFr0ci: TAACAGGC at 3997, TCCTAGGC at 3715, TCTGTGGC at 3671, CCCCTGGC at 3642, CGGGTGGC at 3424, CAGTAGGC at 3290, CCGCAGGC at 3245, CGCCAGGC at 2838, TCCCTGGC at 2436, CGCTAGGC at 2124, TATGTGGC at 2065, TGTCAGGC at 2030, TCTTTGGC at 1347, CGTCAGGC at 787, CAGCAGGC at 582, TAACTGGC at 138.
7. USFr2ci: TAAGTGGC at 3681, CAAGAGGC at 3606, TATTAGGC at 3522, CCAAAGGC at 3263, CATAAGGC at 3255, TCACTGGC at 1728, TACCAGGC at 1221, CCATAGGC at 975, CATAAGGC at 870, CCGGTGGC at 817, TCCATGGC at 772, CCGTTGGC at 613, CCTGTGGC at 460, CAAATGGC at 429, CAAAAGGC at 111.
8. USFr4ci: CCCCTGGC at 3232, TATGTGGC at 2983, TCGCAGGC at 2804, TGGATGGC at 1904, CCCCTGGC at 1482, CGTGTGGC at 1457, CAAATGGC at 1365, TAATTGGC at 709, TGGTAGGC at 688, CCCATGGC at 637.
9. USFr6ci: CAACAGGC at 4045, CACCAGGC at 3912, TCGTAGGC at 3722, TCAGTGGC at 3134, TGGGTGGC at 2157, CGAGTGGC at 2091, CCAATGGC at 1958, TACATGGC at 1894, CGGCAGGC at 1565, TCCCAGGC at 1400, CCCCAGGC at 685, TGAATGGC at 251, TGCCAGGC at 84.
10. USFr8ci: CCCATGGC at 3257, CGATTGGC at 3240, CCAATGGC at 2423, TCCCTGGC at 2354, TATTTGGC at 2334, CCCGAGGC at 2282, TCGAAGGC at 1883, CCTATGGC at 1781, TCTGTGGC at 1715, TCAAAGGC at 937, CAGTAGGC at 258.

USF analysis and results

Main article: Complex locus A1BG and ZNF497 § USFs

"GCCATCTG, which contains a consensus sequence, CANNTG", + "GCCACCGG." which suggests GCCANN(G/T)G. Adding in a portion in the rat insulin 2 gene the equivalent sequence is GCCACCCA yields GCCANN(C/G/T)(A/G).

Using the two versions of the consensus sequence and "⌘F" to locate these sequences in the nucleotides for A1BG listed in A1BG gene transcriptions revealed two occurrences (GCCTGGGA) and (GCCTTCCG) on the ZNF497 side. Combining these with GCCANN(C/G/T)(A/G) suggests GCC(A/T)NN(C/G/T)(A/G).

Reals or randoms	Promoters	direction	Numbers	Strands	Occurrences	Averages (± 0.1)
Reals	UTR	negative	19,13	2	9.5,6.5	9.5 ± 8.5 (--1,+-18),6.5 ± 6.5 (--0,+-13)
Randoms	UTR	arbitrary negative	51	10	5.1	4.75 ± 0.35
Randoms	UTR	alternate negative	44	10	4.4	4.75 ± 0.35
Reals	Core	negative	0	2	0	0
Randoms	Core	arbitrary negative	1	10	0.1	0.1
Randoms	Core	alternate negative	1	10	0.1	0.1
Reals	Core	positive	1	2	0.5	0.5 ± 0.5 (-+1,++0)
Randoms	Core	arbitrary positive	5	10	0.5	0.55 ± 0.05
Randoms	Core	alternate positive	6	10	0.6	0.55
Reals	Proximal	negative	1	2	0.5	0.5 ± 0.5 (+-1,--0)
Randoms	Proximal	arbitrary negative	3	10	0.3	0.5 ± 0.2
Randoms	Proximal	alternate negative	7	10	0.7	0.5 ± 0.2
Reals	Proximal	positive	3	2	1.5	1.5 ± 1.5 (-+3,++0)
Randoms	Proximal	arbitrary positive	3	10	0.3	0.55 ± 0.25
Randoms	Proximal	alternate positive	8	10	0.8	0.55 ± 0.25
Reals	Distal	negative	33	2	16.5	16.5 ± 6.5 (--10,+-23)
Randoms	Distal	arbitrary negative	89	10	8.9	8.45 ± 0.45
Randoms	Distal	alternate negative	80	10	8.0	8.45 ± 0.45
Reals	Distal	positive	63	2	31.5	31.5 ± 13.5 (-+45,++18)
Randoms	Distal	arbitrary positive	124	10	12.4	12.7 ± 0.3
Randoms	Distal	alternate positive	130	10	13.0	12.7 ± 0.3

Comparison:

The occurrences of real USF UTRs are outside the randoms, core, proximals and distals are greater than the randoms. This suggests that the real USFs are likely active or activable.

See also

• M box gene transcriptions