Vitamin D response element gene transcriptions
Vitamin D response elements (VDRE) typically consist of two conserved hexameric half-sites separated by a three nucleotide spacer, referred to as a DR3 type element. Although it is known that the sequence of a VDRE can have a strong influence on the degree of protein binding, particularly at the fifth position in the half-site, previous studies have focused on synthetic variations of response elements and not naturally occurring sequences.
The VDR is widely distributed in tissues, and is not restricted to those tissues considered the classic targets of vitamin D. The VDR upon binding to 1,25(OH)2D heterodimerizes with other nuclear hormone receptors, in particular the family of retinoid X receptors. This complex then binds to special DNA sequences called vitamin D response elements (VDRE) in the promoters of genes which it regulates. A variety of additional proteins called coactivators complex with the activated VDR/RXR heterodimers either to form a bridge from the VDR/RXR complex binding to the VDRE to the proteins responsible for transcription such as RNA polymerase II binding to the transcription start site or to help unravel the chromatin at the site of the gene via recruitment of histone acetyl transferases (HAT), allowing transcription to proceed.

# Human genes

# Consensus sequences
"The following VDRE oligonucleotides were used: mouse osteopontin, 5-GCTCGGGTAGGGTTCACGAGGTTCACTCGACTCG-3; DR3, 5-GCTCGGGTAGAGGTCAAGGAGGTCACTCGACTCG-3; DR3, 5-GCTCGGGTAGAGTTCAAGGAGTTCACTCGACTCG-3; human osteocalcin, 5-GCTCGGGTAGGGGTGACTCACCGGGTGAACGGGGGCATCTCGACTCG-3; and Random, 5-GCTCGGGTAGCTAATCCGTTTCGAGCTCGACTCG-3."
"Using the Jasper and Consite algorithms, the A/GGG/TTCAnnnA/GGG/TTCA and GA/GGTTCATnnnGTTCA sequences were considered as human and mouse VDRE consensus sequences, respectively, as previously shown.17, 18 Previous studies have suggested that regulatory VDREs could locate distally, i.e. > 1 Mb, to the transcription starting site.19 We analysed the entire genomic sequence of the human and murine HOTAIR and ANRIL genes as well as 5 kb upstream the transcription starting sites to include proximal promoter regions. Our analysis revealed two and three potential VDREs in the human HOTAIR and ANRIL genes, respectively, all of them were located within the intron 1 ."
Consensus sequences: (A/G)G(G/T)TCA (human) and G(A/G)GTTCAT (mouse) in (A/G)G(G/T)TCANNN(A/G)G(G/T)TCA and G(A/G)GTTCATNNNGTTCA.

# VDRE samplings
Copying the consensus of the VDRE: (A/G)G(G/T)TCA and putting the sequence in "F" finds no locations for this sequence between ZSCAN22 and A1BG but there three between ZNF497 and A1BG as can be found by the computer programs.
For the Basic programs testing consensus sequence (A/G)G(G/T)TCA (starting with SuccessablesVDRE.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:
- negative strand, negative direction, looking for (A/G)G(G/T)TCA, 2, AGGTCA at 1532, AGGTCA at 1352.
- positive strand, negative direction, looking for (A/G)G(G/T)TCA, 12, AGGTCA at 4307, AGTTCA at 4176, AGTTCA at 4025, AGGTCA at 2585, AGGTCA at 2248, AGTTCA at 1178, AGGTCA at 712, AGGTCA at 576, AGGTCA at 568, AGGTCA at 439, AGTTCA at 254, GGGTCA at 206.
- positive strand, positive direction, looking for (A/G)G(G/T)TCA, 7, GGGTCA at 3379, GGGTCA at 3082, AGTTCA at 2616, GGTTCA at 2594, AGTTCA at 2509, GGGTCA at 2024, GGGTCA at 1250.
- negative strand, positive direction, looking for (A/G)G(G/T)TCA, 5, AGGTCA at 4269, AGTTCA at 4201, GGGTCA at 3820, AGGTCA at 2220, AGGTCA at 153.
- complement, negative strand, negative direction, looking for (C/T)C(A/C)AGT, 12, TCCAGT at 4307, TCAAGT at 4176, TCAAGT at 4025, TCCAGT at 2585, TCCAGT at 2248, TCAAGT at 1178, TCCAGT at 712, TCCAGT at 576, TCCAGT at 568, TCCAGT at 439, TCAAGT at 254, CCCAGT at 206.
- complement, positive strand, negative direction, looking for (C/T)C(A/C)AGT, 2, TCCAGT at 1532, TCCAGT at 1352.
- complement, positive strand, positive direction, looking for (C/T)C(A/C)AGT, 5, TCCAGT at 4269, TGAAGT at 4201, CCCAGT at 3820, TCCAGT at 2220, TCCAGT at 153.
- complement, negative strand, positive direction, looking for (C/T)C(A/C)AGT, 7, CCCAGT at 3379, CCCAGT at 3082, TCAAGT at 2616, CCAAGT at 2594, ACTAGT at 2509, CCCAGT at 2024, CCCAGT at 1250.
- inverse complement, negative strand, negative direction, looking for TGA(A/C)C(C/T), 11, TGAACC at 4268, TGAACT at 4012, TGACCC at 3750, TGAACT at 3242, TGAACT at 3103, TGAACC at 2921, TGAACT at 2580, TGAACT at 2127, TGAACC at 1927, TGAACT at 1300, TGAACC at 328.
- inverse complement, positive strand, negative direction, looking for TGA(A/C)C(C/T), 8, TGAACC at 3784, TGAACC at 3245, TGAACC at 2717, TGAACC at 2382, TGAACC at 1956, TGAACC at 1303, TGAACC at 1012, TGAACC at 846.
- inverse complement, positive strand, positive direction, looking for TGA(A/C)C(C/T), 3, TGAACT at 4016, TGACCC at 1954, TGACCC at 348.
- inverse complement, negative strand, positive direction, looking for TGA(A/C)C(C/T), 6, TGACCC at 4217, TGACCT at 4019, TGAACC at 3937, TGAACC at 3838, TGACCA at 3785, TGACCC at 1663.
- inverse negative strand, negative direction, looking for ACT(G/T)G(A/G), 8, ACTTGG at 3784, ACTTGG at 3245, ACTTGG at 2717, ACTTGG at 2382, ACTTGG at 1956, ACTTGG at 1303, ACTTGG at 1012, ACTTGG at 846.
- inverse positive strand, negative direction, looking for ACT(G/T)G(A/G), 11, ACTTGG at 4268, ACTTGA at 4012, ACTGGG at 3750, ACTTGA at 3242, ACTTGA at 3103, ACTTGG at 2921, ACTTGA at 2580, ACTTGA at 2127, ACTTGG at 1927, ACTTGA at 1300, ACTTGG at 328.
- inverse positive strand, positive direction, looking for ACT(G/T)G(A/G), 6, ACTGGG at 4217, ACTGGA at 4019, ACTTGG at 3937, ACTTGG at 3838, ACTGGA at 3785, ACTGGG at 1663.
- inverse negative strand, positive direction, looking for ACT(G/T)G(A/G), 3, ACTTGA at 4016, ACTGGG at 1954, ACTGGG at 348.

## VDRE (4560-2846) UTRs
- Negative strand, negative direction: TGAACC at 4268, TGAACT at 4012, TGACCC at 3750, TGAACT at 3242, TGAACT at 3103, TGAACC at 2921.
- Positive strand, negative direction: AGGTCA at 4307, AGTTCA at 4176, AGTTCA at 4025.
- Positive strand, negative direction: TGAACC at 3784, TGAACC at 3245.

## VDRE positive direction (4445-4265) core promoters
- Negative strand, positive direction: AGGTCA at 4269.

## VDRE negative direction (2811-2596) proximal promoters
- Positive strand, negative direction: TGAACC at 2717.

## VDRE positive direction (4265-4050) proximal promoters
- Negative strand, positive direction: AGTTCA at 4201.
- Negative strand, positive direction: TGACCC at 4217.

## VDRE negative direction (2596-1) distal promoters
- Negative strand, negative direction: AGGTCA at 1532, AGGTCA at 1352.
- Negative strand, negative direction: TGAACT at 2580, TGAACT at 2127, TGAACC at 1927, TGAACT at 1300, TGAACC at 328.
- Positive strand, negative direction: AGGTCA at 2585, AGGTCA at 2248, AGTTCA at 1178, AGGTCA at 712, AGGTCA at 576, AGGTCA at 568, AGGTCA at 439, AGTTCA at 254, GGGTCA at 206.
- Positive strand, negative direction: TGAACC at 2382, TGAACC at 1956, TGAACC at 1303, TGAACC at 1012, TGAACC at 846.

## VDRE positive direction (4050-1) distal promoters
- Negative strand, positive direction: GGGTCA at 3820, AGGTCA at 2220, AGGTCA at 153.
- Negative strand, positive direction: TGACCT at 4019, TGAACC at 3937, TGAACC at 3838, TGACCA at 3785, TGACCC at 1663.
- Positive strand, positive direction: GGGTCA at 3379, GGGTCA at 3082, AGTTCA at 2616, GGTTCA at 2594, AGTTCA at 2509, GGGTCA at 2024, GGGTCA at 1250.
- Positive strand, positive direction: TGAACT at 4016, TGACCC at 1954, TGACCC at 348.

# VDRE random dataset samplings
- VDREr0: 4, GGGTCA at 3832, AGTTCA at 2458, GGTTCA at 885, AGGTCA at 699.
- VDREr1: 3, GGGTCA at 2777, AGGTCA at 1750, AGTTCA at 561.
- VDREr2: 9, AGGTCA at 4381, GGGTCA at 3905, AGGTCA at 3163, GGTTCA at 2661, GGGTCA at 2185, GGTTCA at 1085, GGGTCA at 467, GGGTCA at 141, GGTTCA at 105.
- VDREr3: 4, GGTTCA at 2323, AGGTCA at 2303, GGGTCA at 1631, GGTTCA at 858.
- VDREr4: 5, GGGTCA at 3806, AGTTCA at 3439, GGTTCA at 3149, GGTTCA at 2373, GGTTCA at 1144.
- VDREr5: 4, AGGTCA at 4296, GGGTCA at 4051, GGTTCA at 2985, GGGTCA at 2696.
- VDREr6: 4, GGTTCA at 4354, GGGTCA at 1832, AGTTCA at 144, GGGTCA at 60.
- VDREr7: 5, AGTTCA at 3748, AGTTCA at 1753, GGGTCA at 972, GGGTCA at 634, GGTTCA at 257.
- VDREr8: 2, AGTTCA at 2794, AGTTCA at 1372.
- VDREr9: 4, GGTTCA at 4550, GGGTCA at 3055, AGTTCA at 1879, GGTTCA at 413.
- VDREr0ci: 4, TGACCC at 4381, TGAACT at 3230, TGAACC at 1692, TGAACT at 1331.
- VDREr1ci: 2, TGACCC at 3052, TGAACC at 392.
- VDREr2ci: 5, TGACCC at 3756, TGACCC at 3543, TGAACC at 3144, TGAACC at 3062, TGACCC at 854.
- VDREr3ci: 5, TGACCT at 4439, TGAACC at 3172, TGACCC at 3103, TGACCT at 2443, TGAACT at 716.
- VDREr4ci: 2, TGACCC at 2893, TGACCC at 345.
- VDREr5ci: 6, TGAACC at 4045, TGAACC at 3941, TGAACT at 3798, TGAACC at 2869, TGACCT at 2538, TGAACC at 63.
- VDREr6ci: 4, TGAACC at 3702, TGACCC at 3521, TGAACT at 3096, TGAACC at 2425.
- VDREr7ci: 5, TGACCT at 3801, TGAACC at 3135, TGAACC at 1973, TGAACC at 1867, TGACCC at 899.
- VDREr8ci: 9, TGAACC at 4455, TGAACC at 3797, TGAACC at 2258, TGAACC at 1583, TGAACT at 1342, TGACCC at 1242, TGACCC at 777, TGACCT at 540, TGACCC at 510.
- VDREr9ci: 2, TGAACC at 2220, TGAACT at 279.

## VDREr arbitrary (evens) (4560-2846) UTRs
- VDREr0: GGGTCA at 3832.
- VDREr2: AGGTCA at 4381, GGGTCA at 3905, AGGTCA at 3163.
- VDREr4: GGGTCA at 3806, AGTTCA at 3439, GGTTCA at 3149.
- VDREr6: GGTTCA at 4354.
- VDREr2ci: TGACCC at 3756, TGACCC at 3543, TGAACC at 3144, TGAACC at 3062.
- VDREr4ci: TGACCC at 2893.
- VDREr6ci: TGAACC at 3702, TGACCC at 3521, TGAACT at 3096.
- VDREr8ci: TGAACC at 4455, TGAACC at 3797.

## VDREr alternate (odds) (4560-2846) UTRs
- VDREr5: AGGTCA at 4296, GGGTCA at 4051, GGTTCA at 2985.
- VDREr7: AGTTCA at 3748.
- VDREr9: GGTTCA at 4550, GGGTCA at 3055.
- VDREr1ci: TGACCC at 3052.
- VDREr3ci: TGACCT at 4439, TGAACC at 3172, TGACCC at 3103.
- VDREr5ci: TGAACC at 4045, TGAACC at 3941, TGAACT at 3798, TGAACC at 2869.
- VDREr7ci: TGACCT at 3801, TGAACC at 3135.

## VDREr arbitrary positive direction (odds) (4445-4265) core promoters
- VDREr5: AGGTCA at 4296.
- VDREr3ci: TGACCT at 4439.

## VDREr alternate positive direction (evens) (4445-4265) core promoters
- VDREr2: AGGTCA at 4381.
- VDREr6: GGTTCA at 4354.

## VDREr arbitrary negative direction (evens) (2811-2596) proximal promoters
- VDREr2: GGTTCA at 2661.
- VDREr8: AGTTCA at 2794.

## VDREr alternate negative direction (odds) (2811-2596) proximal promoters
- VDREr1: GGGTCA at 2777.
- VDREr5: GGGTCA at 2696.

## VDREr arbitrary positive direction (odds) (4265-4050) proximal promoters
- VDREr5: GGGTCA at 4051.

## VDREr arbitrary negative direction (evens) (2596-1) distal promoters
- VDREr0: AGTTCA at 2458, GGTTCA at 885, AGGTCA at 699.
- VDREr2: GGGTCA at 2185, GGTTCA at 1085, GGGTCA at 467, GGGTCA at 141, GGTTCA at 105.
- VDREr4: GGTTCA at 2373, GGTTCA at 1144.
- VDREr6: GGGTCA at 1832, AGTTCA at 144, GGGTCA at 60.
- VDREr8: AGTTCA at 1372.
- VDREr2ci: TGACCC at 854.
- VDREr4ci: TGACCC at 345.
- VDREr6ci: TGAACC at 2425.
- VDREr8ci: TGAACC at 2258, TGAACC at 1583, TGAACT at 1342, TGACCC at 1242, TGACCC at 777, TGACCT at 540, TGACCC at 510.

## VDREr alternate negative direction (odds) (2596-1) distal promoters
- VDREr1: AGGTCA at 1750, AGTTCA at 561.
- VDREr3: GGTTCA at 2323, AGGTCA at 2303, GGGTCA at 1631, GGTTCA at 858.
- VDREr7: AGTTCA at 1753, GGGTCA at 972, GGGTCA at 634, GGTTCA at 257.
- VDREr9: AGTTCA at 1879, GGTTCA at 413.
- VDREr1ci: TGAACC at 392.
- VDREr3ci: TGACCT at 2443, TGAACT at 716.
- VDREr5ci: TGACCT at 2538, TGAACC at 63.
- VDREr7ci: TGAACC at 1973, TGAACC at 1867, TGACCC at 899.
- VDREr9ci: TGAACC at 2220, TGAACT at 279.

## VDREr arbitrary positive direction (odds) (4050-1) distal promoters
- VDREr1: GGGTCA at 2777, AGGTCA at 1750, AGTTCA at 561.
- VDREr3: GGTTCA at 2323, AGGTCA at 2303, GGGTCA at 1631, GGTTCA at 858.
- VDREr5: GGTTCA at 2985, GGGTCA at 2696.
- VDREr7: AGTTCA at 3748, AGTTCA at 1753, GGGTCA at 972, GGGTCA at 634, GGTTCA at 257.
- VDREr9: GGGTCA at 3055, AGTTCA at 1879, GGTTCA at 413.
- VDREr1ci: TGACCC at 3052, TGAACC at 392.
- VDREr3ci: TGAACC at 3172, TGACCC at 3103, TGACCT at 2443, TGAACT at 716.
- VDREr5ci: TGAACC at 4045, TGAACC at 3941, TGAACT at 3798, TGAACC at 2869, TGACCT at 2538, TGAACC at 63.
- VDREr7ci: TGACCT at 3801, TGAACC at 3135, TGAACC at 1973, TGAACC at 1867, TGACCC at 899.
- VDREr9ci: TGAACC at 2220, TGAACT at 279.

## VDREr alternate positive direction (evens) (4050-1) distal promoters
- VDREr0: GGGTCA at 3832, AGTTCA at 2458, GGTTCA at 885, AGGTCA at 699.
- VDREr2: GGGTCA at 3905, AGGTCA at 3163, GGTTCA at 2661, GGGTCA at 2185, GGTTCA at 1085, GGGTCA at 467, GGGTCA at 141, GGTTCA at 105.
- VDREr4: GGGTCA at 3806, AGTTCA at 3439, GGTTCA at 3149, GGTTCA at 2373, GGTTCA at 1144.
- VDREr6: GGGTCA at 1832, AGTTCA at 144, GGGTCA at 60.
- VDREr8: AGTTCA at 2794, AGTTCA at 1372.
- VDREr2ci: TGACCC at 3756, TGACCC at 3543, TGAACC at 3144, TGAACC at 3062, TGACCC at 854.
- VDREr4ci: TGACCC at 2893, TGACCC at 345.
- VDREr6ci: TGAACC at 3702, TGACCC at 3521, TGAACT at 3096, TGAACC at 2425.
- VDREr8ci: TGAACC at 3797, TGAACC at 2258, TGAACC at 1583, TGAACT at 1342, TGACCC at 1242, TGACCC at 777, TGACCT at 540, TGACCC at 510.

# VDRE analysis and results
Consensus sequences: (A/G)G(G/T)TCA (human).
Comparison:
The occurrences of real VDRE UTRs, cores, proximals and distals are greater than the randoms. This suggests that the real VDREs are likely active or activable.

# VDRE2 samplings
Copying a responsive elements consensus sequence GGGTCACACG and putting the sequence in "F" finds none between ZNF497 and A1BG or GGTTCA none between ZSCAN22 and A1BG as can be found by the computer programs.
For the Basic programs testing consensus sequence (A/G)G(G/T)TCANNN(A/G)G(G/T)TCA (starting with SuccessablesVDRE2.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:
- negative strand, negative direction, looking for (A/G)G(G/T)TCANNN(A/G)G(G/T)TCA, 0.
- positive strand, negative direction, looking for (A/G)G(G/T)TCANNN(A/G)G(G/T)TCA, 0.
- positive strand, positive direction, looking for (A/G)G(G/T)TCANNN(A/G)G(G/T)TCA, 0.
- negative strand, positive direction, looking for (A/G)G(G/T)TCANNN(A/G)G(G/T)TCA, 0.
- complement, negative strand, negative direction, looking for (C/T)C(A/C)AGTNNN(C/T)C(A/C)AGT, 0.
- complement, positive strand, negative direction, looking for (C/T)C(A/C)AGTNNN(C/T)C(A/C)AGT, 0.
- complement, positive strand, positive direction, looking for (C/T)C(A/C)AGTNNN(C/T)C(A/C)AGT, 0.
- complement, negative strand, positive direction, looking for (C/T)C(A/C)AGTNNN(C/T)C(A/C)AGT, 0.
- inverse complement, negative strand, negative direction, looking for TGA(A/C)C(C/T)NNNTGA(A/C)C(C/T), 0.
- inverse complement, positive strand, negative direction, looking for TGA(A/C)C(C/T)NNNTGA(A/C)C(C/T), 0.
- inverse complement, positive strand, positive direction, looking for TGA(A/C)C(C/T)NNNTGA(A/C)C(C/T), 0.
- inverse complement, negative strand, positive direction, looking for TGA(A/C)C(C/T)NNNTGA(A/C)C(C/T), 0.
- inverse negative strand, negative direction, looking for ACT(G/T)G(A/G)NNNACT(G/T)G(A/G), 0.
- inverse positive strand, negative direction, looking for ACT(G/T)G(A/G)NNNACT(G/T)G(A/G), 0.
- inverse positive strand, positive direction, looking for ACT(G/T)G(A/G)NNNACT(G/T)G(A/G), 0.
- inverse negative strand, positive direction, looking for ACT(G/T)G(A/G)NNNACT(G/T)G(A/G), 0.

# Acknowledgements
The content on this page was first contributed by: Henry A. Hoff.