Xenobiotic response element gene transcriptions

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

The classical recognition motif of the AhR/ARNT complex, referred to as either the AhR-, dioxin- or xenobiotic- responsive element (AHRE, DRE or XRE), contains the core sequence 5'-GCGTG-3'.[1]

The AhR/ARNT heterodimer directly binds the AHRE/DRE/XRE core sequence in an asymmetric manner such that ARNT binds to 5'-GTG-3' and AhR binding 5'-TC/TGC-3'.[2][3][4]

Human genes

Consensus sequences

The classical recognition motif of the AhR/ARNT complex, referred to as either the AhR-, dioxin- or xenobiotic- responsive element (AHRE, DRE or XRE) has the consensus sequence 5'-(T/G)NGCGTG(A/C)(G/C)A-3'[5][6] in the promoter region of AhR responsive genes.

"Sequence alignment of the mouse CYPIA1 upstream DREs has revealed a consensus sequence [...] which contains an invariant 6-bp core sequence, TNGCGTG, and several variable nucleotides flanking this core that we have previously shown to be important for TCDD-AhR-DRE complex formation (Denison et al., 1988a)."[6]

The quinone reductase (QRDRE) gene contains TCCCCTTGCGTG which has the DRE core of TNGCGTG.[6]

AHRE samplings

Main article: Model samplings

Copying a responsive elements consensus sequence (G/T)NGCGTG(A/C)(C/G)A and putting the sequence in "⌘F" finds none between ZNF497 and A1BG or none between ZSCAN22 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence (G/T)NGCGTG(A/C)(C/G)A (starting with SuccessablesAHRE.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, looking for (G/T)NGCGTG(A/C)(C/G)A, 0.
  2. positive strand, negative direction, looking for (G/T)NGCGTG(A/C)(C/G)A, 0.
  3. positive strand, positive direction, looking for (G/T)NGCGTG(A/C)(C/G)A, 0.
  4. negative strand, positive direction, looking for (G/T)NGCGTG(A/C)(C/G)A, 0.
  5. complement, negative strand, negative direction, looking for (A/C)NCGCAC(G/T)(C/G)T, 0.
  6. complement, positive strand, negative direction, looking for (A/C)NCGCAC(G/T)(C/G)T, 0.
  7. complement, positive strand, positive direction, looking for (A/C)NCGCAC(G/T)(C/G)T, 0.
  8. complement, negative strand, positive direction, looking for (A/C)NCGCAC(G/T)(C/G)T, 0.
  9. inverse complement, negative strand, negative direction, looking for T(C/G)(G/T)CACGCN(A/G), 0.
  10. inverse complement, positive strand, negative direction, looking for T(C/G)(G/T)CACGCN(A/G), 0.
  11. inverse complement, positive strand, positive direction, looking for T(C/G)(G/T)CACGCN(A/G), 0.
  12. inverse complement, negative strand, positive direction, looking for T(C/G)(G/T)CACGCN(A/G), 0.
  13. inverse negative strand, negative direction, looking for A(C/G)(A/C)GTGCGN(G/T), 0.
  14. inverse positive strand, negative direction, looking for A(C/G)(A/C)GTGCGN(G/T), 0.
  15. inverse positive strand, positive direction, looking for A(C/G)(A/C)GTGCGN(G/T), 0.
  16. inverse negative strand, positive direction, looking for A(C/G)(A/C)GTGCGN(G/T), 0.

DIOX samplings

Copying a dioxin-responsive element (DIOX) consensus sequence TNGCGTG and putting the sequence in "⌘F" finds none between ZNF497 and A1BG or none between ZSCAN22 and A1BG as can be found by the computer programs.

A "putative DRE functional consensus sequence from the alignment of functional DREs identified in the flanking regions of the mouse (mDRE1-4), rat (rXREl-2), human (hXREl) CYPIA1, rat glutathione S-transferase Ya (YaDRE), and quinone reductase (QRDRE) genes" is GCGTGNN(A/T)NNN(C/G).[6]

For the Basic programs testing consensus sequence TNGCGTG[6] (starting with SuccessablesDIOX.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, looking for TNGCGTG, 0.
  2. positive strand, negative direction, looking for TNGCGTG, 0.
  3. positive strand, positive direction, looking for TNGCGTG, 2, TGGCGTG at 2565, TCGCGTG at 1131.
  4. negative strand, positive direction, looking for TNGCGTG, 0.
  5. complement, negative strand, negative direction, looking for ANCGCAC, 0.
  6. complement, positive strand, negative direction, looking for ANCGCAC, 0.
  7. complement, positive strand, positive direction, looking for ANCGCAC, 0.
  8. complement, negative strand, positive direction, looking for ANCGCAC, 2, ACCGCAC at 2565, AGCGCAC at 1131.
  9. inverse complement, negative strand, negative direction, looking for CACGCNA, 2, CACGCCA at 2198, CACGCCA at 381.
  10. inverse complement, positive strand, negative direction, looking for CACGCNA, 3, CACGCCA at 3282, CACGCCA at 2209, CACGCCA at 1993.
  11. inverse complement, positive strand, positive direction, looking for CACGCNA, 1, CACGCGA at 1727.
  12. inverse complement, negative strand, positive direction, looking for CACGCNA, 0.
  13. inverse negative strand, negative direction, looking for GTGCGNT, 3, GTGCGGT at 3282, GTGCGGT at 2209, GTGCGGT at 1993.
  14. inverse positive strand, negative direction, looking for GTGCGNT, 2, GTGCGGT at 2198, GTGCGGT at 381.
  15. inverse positive strand, positive direction, looking for GTGCGNT, 0.
  16. inverse negative strand, positive direction, looking for GTGCGNT, 1, GTGCGCT at 1727.

DIOX (4560-2846) UTRs

  1. Positive strand, negative direction: CACGCCA at 3282.

DIOX negative direction (2596-1) distal promoters

  1. Negative strand, negative direction: CACGCCA at 2198, CACGCCA at 381.
  2. Positive strand, negative direction: CACGCCA at 2209, CACGCCA at 1993.

DIOX positive direction (4050-1) distal promoters

  1. Positive strand, positive direction: TGGCGTG at 2565, CACGCGA at 1727, TCGCGTG at 1131.

DIOX random dataset samplings

  1. DIOXr0: 1, TTGCGTG at 1379.
  2. DIOXr1: 0.
  3. DIOXr2: 2, TAGCGTG at 2458, TCGCGTG at 591.
  4. DIOXr3: 0.
  5. DIOXr4: 0.
  6. DIOXr5: 0.
  7. DIOXr6: 0.
  8. DIOXr7: 0.
  9. DIOXr8: 0.
  10. DIOXr9: 0.
  11. DIOXr0ci: 2, CACGCTA at 3734, CACGCAA at 663.
  12. DIOXr1ci: 0.
  13. DIOXr2ci: 1, CACGCCA at 1469.
  14. DIOXr3ci: 1, CACGCTA at 178.
  15. DIOXr4ci: 0.
  16. DIOXr5ci: 3, CACGCCA at 3473, CACGCGA at 2701, CACGCCA at 79.
  17. DIOXr6ci: 0.
  18. DIOXr7ci: 0.
  19. DIOXr8ci: 1, CACGCGA at 16.
  20. DIOXr9ci: 0.

DIOXr arbitrary (evens) (4560-2846) UTRs

  1. DIOXr0ci: CACGCTA at 3734.

DIOXr alternate (odds) (4560-2846) UTRs

  1. DIOXr5ci: CACGCCA at 3473.

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

  1. DIOXr5ci: CACGCGA at 2701.

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

  1. DIOXr0: TTGCGTG at 1379.
  2. DIOXr2: TAGCGTG at 2458, TCGCGTG at 591.
  3. DIOXr0ci: CACGCAA at 663.
  4. DIOXr2ci: CACGCCA at 1469.
  5. DIOXr8ci: CACGCGA at 16.

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

  1. DIOXr3ci: CACGCTA at 178.
  2. DIOXr5ci: CACGCCA at 79.

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

  1. DIOXr3ci: CACGCTA at 178.
  2. DIOXr5ci: CACGCCA at 3473, CACGCGA at 2701, CACGCCA at 79.

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

  1. DIOXr0: TTGCGTG at 1379.
  2. DIOXr2: TAGCGTG at 2458, TCGCGTG at 591.
  3. DIOXr0ci: CACGCTA at 3734, CACGCAA at 663.
  4. DIOXr2ci: CACGCCA at 1469.
  5. DIOXr8ci: CACGCGA at 16.

DIOX analysis and results

Main article: Complex locus A1BG and ZNF497 § DIOXs

"The DRE consensus sequence, 5′-TNGCGTG-3′ is conserved throughout most species and occurs in multiples within the promoter of a target gene [1, 4]."[7]

"Sequence alignment of the mouse CYPIA1 upstream DREs has revealed a consensus sequence [...] which contains an invariant 6-bp core sequence, TNGCGTG, and several variable nucleotides flanking this core that we have previously shown to be important for TCDD-AhR-DRE complex formation (Denison et al., 1988a)."[6]

The dioxin response element occurs in the UTR between ZSCAN22 and A1BG on the positive strand, negative direction CACGCCA, the complement inverse, at 3282. It also occurs in the distal promoters, both in the negative direction and has three occurrences on the positive strand, positive direction for a total of eight occurrences in four strands for 2.0.

With the twenty random datasets, there are only eleven occurrences for 0.55, which suggests these DREs are likely active or activable. The random occurrences were also in the UTR (one) and distal promoters (10).

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 1 2 0.5 0.5 ± 0.5 (--0,+-1)
Randoms UTR arbitrary negative 1 10 0.1 0.1
Randoms UTR alternate negative 1 10 0.1 0.1
Reals Core negative 0 2 0 0
Randoms Core arbitrary negative 0 10 0 0
Randoms Core alternate negative 0 10 0 0
Reals Core positive 0 2 0 0
Randoms Core arbitrary positive 0 10 0 0
Randoms Core alternate positive 0 10 0 0
Reals Proximal negative 0 2 0 0
Randoms Proximal arbitrary negative 0 10 0 0.05
Randoms Proximal alternate negative 1 10 0.1 0.05
Reals Proximal positive 0 2 0 0
Randoms Proximal arbitrary positive 0 10 0 0
Randoms Proximal alternate positive 0 10 0 0
Reals Distal negative 4 2 2 2 ± 0 (--2,+-2)
Randoms Distal arbitrary negative 6 10 0.6 0.4
Randoms Distal alternate negative 2 10 0.2 0.4
Reals Distal positive 3 2 1.5 1.5 ± 1.5 (-+0,++3)
Randoms Distal arbitrary positive 4 10 0.4 0.55
Randoms Distal alternate positive 7 10 0.7 0.55

Comparison:

The occurrences of real DIOXs are greater than the randoms. This suggests that the real DIOXs are likely active or activable.

Xenobiotic response element samplings

"The megalin (LRP2) gene promoter region [shows] eight consensus sequence of XRE 5′-GCGTG-3′."[8]

"The AHR-ARNT heterodimer then binds to the xenobiotic response element (XRE), defined by the consensus 5′-GCGTG-3′ motif, within the promoter region of target genes to activate transcription."[9]

Copying a responsive elements consensus sequence GCGTG and putting the sequence in "⌘F" finds six between ZNF497 and A1BG or none between ZSCAN22 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence GCGTG (starting with SuccessablesXRE.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, looking for GCGTG, 0.
  2. positive strand, negative direction, looking for GCGTG, 4, GCGTG at 3046, GCGTG at 1896, GCGTG at 1243, GCGTG at 740.
  3. positive strand, positive direction, looking for GCGTG, 13, GCGTG at 2565, GCGTG at 1555, GCGTG at 1551, GCGTG at 1299, GCGTG at 1135, GCGTG at 1131, GCGTG at 1051, GCGTG at 1047, GCGTG at 977, GCGTG at 877, GCGTG at 799, GCGTG at 795, GCGTG at 685.
  4. negative strand, positive direction, looking for GCGTG, 6, GCGTG at 2554, GCGTG at 1719, GCGTG at 1242, GCGTG at 1216, GCGTG at 1019, GCGTG at 544.
  5. complement, negative strand, negative direction, looking for CGCAC, 4, CGCAC at 3046, CGCAC at 1896, CGCAC at 1243, CGCAC at 740.
  6. complement, positive strand, negative direction, looking for CGCAC, 0.
  7. complement, positive strand, positive direction, looking for CGCAC, 6, CGCAC at 2554, CGCAC at 1719, CGCAC at 1242, CGCAC at 1216, CGCAC at 1019, CGCAC at 544.
  8. complement, negative strand, positive direction, looking for CGCAC, 13, CGCAC at 2565, CGCAC at 1555, CGCAC at 1551, CGCAC at 1299, CGCAC at 1135, CGCAC at 1131, CGCAC at 1051, CGCAC at 1047, CGCAC at 977, CGCAC at 877, CGCAC at 799, CGCAC at 795, CGCAC at 685.
  9. inverse complement, negative strand, negative direction, looking for CACGC, 3, CACGC at 2196, CACGC at 447, CACGC at 379.
  10. inverse complement, positive strand, negative direction, looking for CACGC, 5, CACGC at 3280, CACGC at 2207, CACGC at 1991, CACGC at 963, CACGC at 663.
  11. inverse complement, positive strand, positive direction, looking for CACGC, 14, CACGC at 1763, CACGC at 1725, CACGC at 1589, CACGC at 1521, CACGC at 1253, CACGC at 1244, CACGC at 1169, CACGC at 1160, CACGC at 1085, CACGC at 1017, CACGC at 665, CACGC at 581, CACGC at 497, CACGC at 488.
  12. inverse complement, negative strand, positive direction, looking for CACGC, 11, CACGC at 1553, CACGC at 1301, CACGC at 1133, CACGC at 1049, CACGC at 987, CACGC at 969, CACGC at 887, CACGC at 869, CACGC at 803, CACGC at 797, CACGC at 776.
  13. inverse negative strand, negative direction, looking for GTGCG, 5, GTGCG at 3280, GTGCG at 2207, GTGCG at 1991, GTGCG at 963, GTGCG at 663.
  14. inverse positive strand, negative direction, looking for GTGCG, 3, GTGCG at 2196, GTGCG at 447, GTGCG at 379.
  15. inverse positive strand, positive direction, looking for GTGCG, 11, GTGCG at 1553, GTGCG at 1301, GTGCG at 1133, GTGCG at 1049, GTGCG at 987, GTGCG at 969, GTGCG at 887, GTGCG at 869, GTGCG at 803, GTGCG at 797, GTGCG at 776.
  16. inverse negative strand, positive direction, looking for GTGCG, 14, GTGCG at 1763, GTGCG at 1725, GTGCG at 1589, GTGCG at 1521, GTGCG at 1253, GTGCG at 1244, GTGCG at 1169, GTGCG at 1160, GTGCG at 1085, GTGCG at 1017, GTGCG at 665, GTGCG at 581, GTGCG at 497, GTGCG at 488.

XRE (4560-2846) UTRs

  1. Positive strand, negative direction: CACGC at 3280, GCGTG at 3046.

XRE negative direction (2596-1) distal promoters

  1. Negative strand, negative direction: CACGC at 2196, CACGC at 447, CACGC at 379.
  2. Positive strand, negative direction: CACGC at 2207, CACGC at 1991, GCGTG at 1896, GCGTG at 1243, CACGC at 963, GCGTG at 740, CACGC at 663

XRE positive direction (4050-1) distal promoters

  1. Negative strand, positive direction: GCGTG at 2554, GCGTG at 1719, CACGC at 1553, CACGC at 1301, GCGTG at 1242, GCGTG at 1216, CACGC at 1133, CACGC at 1049, GCGTG at 1019, CACGC at 987, CACGC at 969, CACGC at 887, CACGC at 869, CACGC at 803, CACGC at 797, CACGC at 776, GCGTG at 544.
  2. Positive strand, positive direction: GCGTG at 2565, CACGC at 1763, CACGC at 1725, CACGC at 1589, GCGTG at 1555, GCGTG at 1551, CACGC at 1521, GCGTG at 1299, CACGC at 1253, CACGC at 1244, CACGC at 1169, CACGC at 1160, GCGTG at 1135, GCGTG at 1131, CACGC at 1085, GCGTG at 1051, GCGTG at 1047, CACGC at 1017, GCGTG at 977, GCGTG at 877, GCGTG at 799, GCGTG at 795, GCGTG at 685, CACGC at 665, CACGC at 581, CACGC at 497, CACGC at 488.

XRE random dataset samplings

  1. XREr0: 4, GCGTG at 3280, GCGTG at 3076, GCGTG at 1379, GCGTG at 1076.
  2. XREr1: 1, GCGTG at 695.
  3. XREr2: 4, GCGTG at 3087, GCGTG at 2458, GCGTG at 1241, GCGTG at 591.
  4. XREr3: 1, GCGTG at 1530.
  5. XREr4: 3, GCGTG at 3732, GCGTG at 1562, GCGTG at 957.
  6. XREr5: 5, GCGTG at 4373, GCGTG at 4314, GCGTG at 3955, GCGTG at 2404, GCGTG at 370.
  7. XREr6: 2, GCGTG at 1335, GCGTG at 658.
  8. XREr7: 6, GCGTG at 3561, GCGTG at 3315, GCGTG at 2296, GCGTG at 1789, GCGTG at 452, GCGTG at 336.
  9. XREr8: 3, GCGTG at 4128, GCGTG at 2273, GCGTG at 303.
  10. XREr9: 2, GCGTG at 1430, GCGTG at 428.
  11. XREr0ci: 2, CACGC at 3732, CACGC at 661.
  12. XREr1ci: 1, CACGC at 2663.
  13. XREr2ci: 4, CACGC at 2926, CACGC at 2252, CACGC at 1929, CACGC at 1467.
  14. XREr3ci: 4, CACGC at 1818, CACGC at 586, CACGC at 176, CACGC at 142.
  15. XREr4ci: 0.
  16. XREr5ci: 8, CACGC at 4134, CACGC at 3471, CACGC at 2699, CACGC at 2676, CACGC at 1788, CACGC at 1099, CACGC at 77, CACGC at 73.
  17. XREr6ci: 2, CACGC at 2172, CACGC at 1673.
  18. XREr7ci: 0.
  19. XREr8ci: 2, CACGC at 1084, CACGC at 14.
  20. XREr9ci: 4, CACGC at 3738, CACGC at 3436, CACGC at 2116, CACGC at 1360.

XREr arbitrary (evens) (4560-2846) UTRs

  1. XREr0: GCGTG at 3280, GCGTG at 3076.
  2. XREr2: GCGTG at 3087.
  3. XREr4: GCGTG at 3732.
  4. XREr6: GCGTG at 1335, GCGTG at 658.
  5. XREr8: GCGTG at 4128.
  6. XREr0ci: CACGC at 3732.
  7. XREr2ci: CACGC at 2926.

XREr alternate (odds) (4560-2846) UTRs

  1. XREr5: GCGTG at 4373, GCGTG at 4314, GCGTG at 3955.
  2. XREr5ci: CACGC at 4134, CACGC at 3471.
  3. XREr9ci: CACGC at 3738, CACGC at 3436.

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

  1. XREr5: GCGTG at 4373, GCGTG at 4314.

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

  1. XREr1ci: CACGC at 2663.
  2. XREr5ci: CACGC at 2699, CACGC at 2676.

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

  1. XREr5ci: CACGC at 4134.

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

  1. XREr8: GCGTG at 4128.

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

  1. XREr0: GCGTG at 1379, GCGTG at 1076.
  2. XREr2: GCGTG at 2458, GCGTG at 1241, GCGTG at 591.
  3. XREr4: GCGTG at 1562, GCGTG at 957.
  4. XREr6: GCGTG at 1335, GCGTG at 658.
  5. XREr8: GCGTG at 2273, GCGTG at 303.
  6. XREr0ci: CACGC at 661.
  7. XREr2ci: CACGC at 2252, CACGC at 1929, CACGC at 1467.
  8. XREr6ci: CACGC at 2172, CACGC at 1673.
  9. XREr8ci: CACGC at 1084, CACGC at 14.

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

  1. XREr1: GCGTG at 695.
  2. XREr3: GCGTG at 1530.
  3. XREr5: GCGTG at 2404, GCGTG at 370.
  4. XREr7: GCGTG at 2296, GCGTG at 1789, GCGTG at 452, GCGTG at 336.
  5. XREr3ci: CACGC at 1818, CACGC at 586, CACGC at 176, CACGC at 142.
  6. XREr5ci: CACGC at 1788, CACGC at 1099, CACGC at 77, CACGC at 73.
  7. XREr9ci: CACGC at 2116, CACGC at 1360.

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

  1. XREr1: GCGTG at 695.
  2. XREr3: GCGTG at 1530.
  3. XREr5: GCGTG at 3955, GCGTG at 2404, GCGTG at 370.
  4. XREr7: GCGTG at 3561, GCGTG at 3315, GCGTG at 2296, GCGTG at 1789, GCGTG at 452, GCGTG at 336.
  5. XREr1ci: CACGC at 2663.
  6. XREr3ci: CACGC at 1818, CACGC at 586, CACGC at 176, CACGC at 142.
  7. XREr5ci: CACGC at 3471, CACGC at 2699, CACGC at 2676, CACGC at 1788, CACGC at 1099, CACGC at 77, CACGC at 73.
  8. XREr9ci: CACGC at 3738, CACGC at 3436, CACGC at 2116, CACGC at 1360.

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

  1. XREr0: GCGTG at 3280, GCGTG at 3076, GCGTG at 1379, GCGTG at 1076.
  2. XREr2: GCGTG at 3087, GCGTG at 2458, GCGTG at 1241, GCGTG at 591.
  3. XREr4: GCGTG at 3732, GCGTG at 1562, GCGTG at 957.
  4. XREr6: GCGTG at 1335, GCGTG at 658.
  5. XREr8: GCGTG at 2273, GCGTG at 303.
  6. XREr0ci: CACGC at 3732, CACGC at 661.
  7. XREr2ci: CACGC at 2926, CACGC at 2252, CACGC at 1929, CACGC at 1467.
  8. XREr6ci: CACGC at 2172, CACGC at 1673.
  9. XREr8ci: CACGC at 1084, CACGC at 14.

XRE analysis and results

Main article: Complex locus A1BG and ZNF497 § XREs

"The megalin (LRP2) gene promoter region [shows] eight consensus sequence of XRE 5′-GCGTG-3′."[8]

A1BG is not included in any of the aryl hydrocarbon receptor (Gene ID: 196) pathways (19).[10] As such the XRE is not expected in the promoters of A1BG.

The XRE is involved in the response of 78 human genes such as Gene ID: 1543 where the "Hypomethylation of the XRE -1383 site is associated with the upregulation of CYP1A1 in gastric adenocarcinoma."[11] "Bisulfite sequencing and the resulting methylation percentages revealed dynamically methylated CpG sites located within or around xenobiotic response elements (XRE) 4–10, and a region of consistent hypermethylation located near proximal promoter, encompassing XRE2-3."[11] For example using search concepts ("gastric adenocarcinoma" A1BG) on Google Scholar produced, "Immunohistochemical staining on a tissue microarray was then carried out for alpha-1B-glycoprotein (A1BG), leucine-rich alpha-2-glycoprotein (LRG1), ubiquitin carboxyl-terminal hydrolase 1 (USP1), and mucin-5B as candidate biomarkers. Their levels were significantly elevated in lung cancer tissue. A1BG levels were also determined as significantly elevated with Western blot on sera samples."[12] Further, "Using sera as samples and multiple fractionation steps (protein depletion, lectin affinity fractionation, IEF separation, and LC-MS analysis), the following candidates were selected as breast cancer-associated proteins: thrombospondin-1 (TSP1) and 5 (TSP5), alpha-1B-glycoprotein (A1BG), serum amyloid P-component (SAP), and tenascin-X (TN-X) [106]. SAP and TSP5 were increased in breast cancer serum, A1BG showed a pI shift and a slight increase in total abundance in the cancer samples, TSP1 showed changes in glycan structure, and TN-X was both increased and showed glycan structure changes."[12]

The xenobiotic response element (XRE) GCGTG occurs twice only on the positive strand in the UTR between ZSCAN22 and A1BG for an occurrence of (1.0), but does not occur in either core promoter or proximal promoter. For the distal promoters it occurs along with its complement inverse ten times between the two strands, negative (3) or positive (7), in the negative direction, and between the two strands negative (17) for 8.5 or positive (27) for 13.5 in the positive direction.

The random datasets contained seven XREs in each of ten UTRs for an occurrence of 0.7, twice in the core promoter in the arbitrarily chosen positive direction for an occurrence of 1.0, once in the proximal direction also in the positive direction for 0.5. In the distal promoters nineteen in the arbitrarily chosen negative direction for ten strands yielding 1.9 occurrences per strand and twenty-seven in the positive direction for ten strands yielding 2.7 occurrences per strand.

Although the occurrences are close for the UTRs (1.0 vs 0.7), the comparisons for the core promoters (0 vs 1.0) and proximal promoters (0 vs 0.5) are not close, and for the distal promoters (5.0 vs 1.9) in the negative direction and (13.5 vs 2.7) in the positive direction are also not close, suggesting that the occurrences of the XREs are likely active or activable rather than random occurrences.

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 2 2 1 1 ± 1 (--0,+-2)
Randoms UTR arbitrary negative 9 10 0.9 0.8
Randoms UTR alternate negative 7 10 0.7 0.8
Reals Core negative 0 2 0 0
Randoms Core arbitrary negative 0 10 0 0
Randoms Core alternate negative 0 10 0 0
Reals Core positive 0 2 0 0
Randoms Core arbitrary positive 2 10 0.2 0.1
Randoms Core alternate positive 0 10 0 0.1
Reals Proximal negative 0 2 0 0
Randoms Proximal arbitrary negative 0 10 0 0.15
Randoms Proximal alternate negative 3 10 0.3 0.15
Reals Proximal positive 0 2 0 0
Randoms Proximal arbitrary positive 1 10 0.1 0.1
Randoms Proximal alternate positive 1 10 0.1 0.1
Reals Distal negative 10 2 5 5 ± 2 (--3,+-7)
Randoms Distal arbitrary negative 19 10 1.9 1.85
Randoms Distal alternate negative 18 10 1.8 1.85
Reals Distal positive 44 2 22 22 ± 5 (-+17,++27)
Randoms Distal arbitrary positive 27 10 2.7 2.6
Randoms Distal alternate positive 25 10 2.5 2.6

Comparison:

The occurrences of real XREs are greater than the randoms. This suggests that the real XREs are likely active or activable.

QRDRE samplings

Copying a responsive elements consensus sequence TCCCCT and putting the sequence in "⌘F" finds none between ZNF497 and A1BG or none between ZSCAN22 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence TCCCCT (starting with SuccessablesQRD.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, looking for TCCCCT, 0.
  2. positive strand, negative direction, looking for TCCCCT, 0.
  3. positive strand, positive direction, looking for TCCCCT, 3, TCCCCT at 3665, TCCCCT at 2657, TCCCCT at 321.
  4. negative strand, positive direction, looking for TCCCCT, 1, TCCCCT at 1073.
  5. complement, negative strand, negative direction, looking for AGGGGA, 0.
  6. complement, positive strand, negative direction, looking for AGGGGA, 0.
  7. complement, positive strand, positive direction, looking for AGGGGA, 1, AGGGGA at 1073.
  8. complement, negative strand, positive direction, looking for AGGGGA, 3, AGGGGA at 3665, AGGGGA at 2657, AGGGGA at 321.
  9. inverse complement, negative strand, negative direction, looking for AGGGGA, 0.
  10. inverse complement, positive strand, negative direction, looking for AGGGGA, 0.
  11. inverse complement, positive strand, positive direction, looking for AGGGGA, 1, AGGGGA at 1073.
  12. inverse complement, negative strand, positive direction, looking for AGGGGA, 3, AGGGGA at 3665, AGGGGA at 2657, AGGGGA at 321.
  13. inverse negative strand, negative direction, looking for TCCCCT, 0.
  14. inverse positive strand, negative direction, looking for TCCCCT, 0.
  15. inverse positive strand, positive direction, looking for TCCCCT, 3, TCCCCT at 3665, TCCCCT at 2657, TCCCCT at 321.
  16. inverse negative strand, positive direction, looking for TCCCCT, 1, TCCCCT at 1073.

QRDRE positive direction (4050-1) distal promoters

  1. Negative strand, positive direction: TCCCCT at 1073.
  2. Positive strand, positive direction: TCCCCT at 3665, TCCCCT at 2657, TCCCCT at 321.

QRDRE random dataset samplings

  1. QRDREr0: 1, TCCCCT at 469.
  2. QRDREr1: 2, TCCCCT at 2209, TCCCCT at 867.
  3. QRDREr2: 2, TCCCCT at 926, TCCCCT at 893.
  4. QRDREr3: 5, TCCCCT at 4055, TCCCCT at 3828, TCCCCT at 3221, TCCCCT at 2496, TCCCCT at 2485.
  5. QRDREr4: 1, TCCCCT at 4446.
  6. QRDREr5: 0.
  7. QRDREr6: 3, TCCCCT at 3602, TCCCCT at 3559, TCCCCT at 49.
  8. QRDREr7: 2, TCCCCT at 3806, TCCCCT at 542.
  9. QRDREr8: 0.
  10. QRDREr9: 2, TCCCCT at 2827, TCCCCT at 2573.
  11. QRDREr0ci: 4, AGGGGA at 2945, AGGGGA at 2794, AGGGGA at 922, AGGGGA at 453.
  12. QRDREr1ci: 2, AGGGGA at 3180, AGGGGA at 1181.
  13. QRDREr2ci: 3, AGGGGA at 1427, AGGGGA at 678, AGGGGA at 662.
  14. QRDREr3ci: 2, AGGGGA at 1625, AGGGGA at 819.
  15. QRDREr4ci: 2, AGGGGA at 2939, AGGGGA at 2209.
  16. QRDREr5ci: 2, AGGGGA at 1810, AGGGGA at 519.
  17. QRDREr6ci: 1, AGGGGA at 2794.
  18. QRDREr7ci: 3, AGGGGA at 4320, AGGGGA at 4295, AGGGGA at 3714.
  19. QRDREr8ci: 1, AGGGGA at 2919.
  20. QRDREr9ci: 2, AGGGGA at 2439, AGGGGA at 2175.

QRDREr arbitrary (evens) (4560-2846) UTRs

  1. QRDREr4: TCCCCT at 4446.
  2. QRDREr6: TCCCCT at 3602, TCCCCT at 3559.
  3. QRDREr0ci: AGGGGA at 2945.
  4. QRDREr4ci: AGGGGA at 2939.
  5. QRDREr8ci: AGGGGA at 2919.

QRDREr alternate (odds) (4560-2846) UTRs

  1. QRDREr3: TCCCCT at 4055, TCCCCT at 3828, TCCCCT at 3221.
  2. QRDREr7: TCCCCT at 3806.
  3. QRDREr1ci: AGGGGA at 3180.
  4. QRDREr7ci: 3, AGGGGA at 4320.

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

  1. QRDREr9: TCCCCT at 2827.

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

  1. QRDREr7ci: AGGGGA at 4320, AGGGGA at 4295.

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

  1. QRDREr0ci: AGGGGA at 2794.

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

  1. QRDREr3: TCCCCT at 4055.

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

  1. QRDREr0: TCCCCT at 469.
  2. QRDREr2: TCCCCT at 926, TCCCCT at 893.
  3. QRDREr6: TCCCCT at 49.
  4. QRDREr0ci: AGGGGA at 922, AGGGGA at 453.
  5. QRDREr2ci: AGGGGA at 1427, AGGGGA at 678, AGGGGA at 662.
  6. QRDREr4ci: AGGGGA at 2209.

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

  1. QRDREr1: TCCCCT at 2209, TCCCCT at 867.
  2. QRDREr3: TCCCCT at 2496, TCCCCT at 2485.
  3. QRDREr7: TCCCCT at 542.
  4. QRDREr9: TCCCCT at 2573.
  5. QRDREr1ci: AGGGGA at 1181.
  6. QRDREr3ci: AGGGGA at 1625, AGGGGA at 819.
  7. QRDREr5ci: AGGGGA at 1810, AGGGGA at 519.
  8. QRDREr9ci: AGGGGA at 2439, AGGGGA at 2175.

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

  1. QRDREr1: TCCCCT at 2209, TCCCCT at 867.
  2. QRDREr3: TCCCCT at 3828, TCCCCT at 3221, TCCCCT at 2496, TCCCCT at 2485.
  3. QRDREr7: TCCCCT at 3806, TCCCCT at 542.
  4. QRDREr9: TCCCCT at 2827, TCCCCT at 2573.
  5. QRDREr1ci: AGGGGA at 3180, AGGGGA at 1181.
  6. QRDREr3ci: AGGGGA at 1625, AGGGGA at 819.
  7. QRDREr5ci: AGGGGA at 1810, AGGGGA at 519.
  8. QRDREr7ci: AGGGGA at 3714.
  9. QRDREr9ci: AGGGGA at 2439, AGGGGA at 2175.

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

  1. QRDREr0: TCCCCT at 469.
  2. QRDREr2: TCCCCT at 926, TCCCCT at 893.
  3. QRDREr6: TCCCCT at 3602, TCCCCT at 3559, TCCCCT at 49.
  4. QRDREr0ci: AGGGGA at 922, AGGGGA at 453.
  5. QRDREr2ci: AGGGGA at 1427, AGGGGA at 678, AGGGGA at 662.
  6. QRDREr4ci: AGGGGA at 2939, AGGGGA at 2209.

QRDRE analysis and results

Main article: Complex locus A1BG and ZNF497 § QRDREs

The quinone reductase (QRDRE) gene contains TCCCCTTGCGTG which has the DRE core of TNGCGTG.[6] TCCCCTTGCGTG is not present in any of the four promoters tested that are juxtaposed to A1BG.

Peroxisome proliferator hormone response elements (PPREs, QRDREs) consensus sequences are AGGGGA and TCCCCT.[6]

While the QRDRE may be just limited to TCCCC since it also has the fixed T after this sequence, TCCCCT has been used to examine the four possible promoters. The only elements are in the distal promoters in the positive direction, negative strand TCCCCT at 1073, and positive strand TCCCCT at 3665, TCCCCT at 2657, TCCCCT at 321, for a response of 1.0.

The random datasets had a far greater number of sequences. In the UTR between ZSCAN22 and A1BG were six consensus sequences, three direct and three complement inverses, for a response of 0.6. In the core promoters there were two in the chosen positive direction for a response of 0.2. The proximal promoters had three, two in the chosen negative direction and one in the positive direction for a response of 0.3. The distal promoters there were ten in the chosen negative direction for 1.0 and nineteen in the positive direction for 1.9.

While the responses for the UTR, core and proximal promoters were low but none were zero. None of the QRDREs are linked to the DREs. As the real occurrences were only in the distal promoters and the occurrences were in the 1.0 to 1.9 range it is likely that these QRDREs are random.

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 0 2 0 0
Randoms UTR arbitrary negative 6 10 0.6 0.6
Randoms UTR alternate negative 6 10 0.6 0.6
Reals Core negative 0 2 0 0
Randoms Core arbitrary negative 0 10 0 0.05
Randoms Core alternate negative 1 10 0.1 0.05
Reals Core positive 0 2 0 0
Randoms Core arbitrary positive 2 10 0.2 0.1
Randoms Core alternate positive 0 10 0 0.1
Reals Proximal negative 0 2 0 0
Randoms Proximal arbitrary negative 1 10 0.1 0.05
Randoms Proximal alternate negative 0 10 0 0.05
Reals Proximal positive 0 2 0 0
Randoms Proximal arbitrary positive 1 10 0.1 0.05
Randoms Proximal alternate positive 0 10 0 0.05
Reals Distal negative 0 2 0 0
Randoms Distal arbitrary negative 10 10 1 1.15
Randoms Distal alternate negative 13 10 1.3 1.15
Reals Distal positive 4 2 2 2 ± 1 (-+1,++3)
Randoms Distal arbitrary positive 19 10 1.9 1.6
Randoms Distal alternate positive 13 10 1.3 1.6

Comparison:

The occurrences of real QRDRE distals are outside the randoms. This suggests that the real QRDREs are likely active or activable.

TCDD*AhR DNA-binding consensus sequence sampling

TCDD*AhR DNA-binding consensus sequence is GCGTGNN(A/T)NNN(C/G).[6]

For the Basic programs testing consensus sequence GCGTGNN(A/T)NNN(C/G) (starting with SuccessablesAhRY.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, looking for GCGTGNN(A/T)NNN(C/G), 0.
  2. positive strand, negative direction, looking for GCGTGNN(A/T)NNN(C/G), 0.
  3. positive strand, positive direction, looking for GCGTGNN(A/T)NNN(C/G), 4, GCGTGCGTGTGC at 1558, GCGTGTGACCAC at 1142, GCGTGCGTGTCG at 1054, GCGTGCGTGTGC at 802.
  4. negative strand, positive direction, looking for GCGTGNN(A/T)NNN(C/G), 1, GCGTGAGTGCGC at 1726.
  5. complement, negative strand, negative direction, looking for CGCACNN(A/T)NNN(C/G), 0.
  6. complement, positive strand, negative direction, looking for CGCACNN(A/T)NNN(C/G), 0.
  7. complement, positive strand, positive direction, looking for CGCACNN(A/T)NNN(C/G), 1, CGCACTCACGCG at 1726.
  8. complement, negative strand, positive direction, looking for CGCACNN(A/T)NNN(C/G), 4, CGCACGCACACG at 1558, CGCACACTGGTG at 1142, CGCACGCACAGC at 1054, CGCACGCACACG at 802.
  9. inverse complement, negative strand, negative direction, looking for (C/G)NNN(A/T)NNCACGC, 0.
  10. inverse complement, positive strand, negative direction, looking for (C/G)NNN(A/T)NNCACGC, 0.
  11. inverse complement, positive strand, positive direction, looking for (C/G)NNN(A/T)NNCACGC, 4, CCGCACTCACGC at 1725, CCGGAAGCACGC at 1521, GAGTACGCACGC at 1244, CCGGAAGCACGC at 1017.
  12. inverse complement, negative strand, positive direction, looking for (C/G)NNN(A/T)NNCACGC, 2, GAAGATCCACGC at 969, GAAGATCCACGC at 869.
  13. inverse negative strand, negative direction, looking for (C/G)NNN(A/T)NNGTGCG, 0.
  14. inverse positive strand, negative direction, looking for (C/G)NNN(A/T)NNGTGCG, 0.
  15. inverse positive strand, positive direction, looking for (C/G)NNN(A/T)NNGTGCG, 2, CTTCTAGGTGCG at 969, CTTCTAGGTGCG at 869.
  16. inverse negative strand, positive direction, looking for (C/G)NNN(A/T)NNGTGCG, 4, GGCGTGAGTGCG at 1725, GGCCTTCGTGCG at 1521, CTCATGCGTGCG at 1244, GGCCTTCGTGCG at 1017.

AhRY positive direction (4050-1) distal promoters

  1. Negative strand, positive direction: GCGTGAGTGCGC at 1726, GAAGATCCACGC at 969, GAAGATCCACGC at 869.
  2. Positive strand, positive direction: CCGCACTCACGC at 1725, GCGTGCGTGTGC at 1558, CCGGAAGCACGC at 1521, GAGTACGCACGC at 1244, GCGTGTGACCAC at 1142, GCGTGCGTGTCG at 1054, CCGGAAGCACGC at 1017, GCGTGCGTGTGC at 802.

TCDD*AhR DNA-binding consensus sequence random dataset samplings

  1. AhRYr0: 0.
  2. AhRYr1: 0.
  3. AhRYr2: 1, GCGTGATTTCCG at 1248.
  4. AhRYr3: 0.
  5. AhRYr4: 2, GCGTGGGTAAAG at 3739, GCGTGGCTTCTG at 964.
  6. AhRYr5: 1, GCGTGATTCGCC at 4380.
  7. AhRYr6: 1, GCGTGTCATGTG at 1342.
  8. AhRYr7: 1, GCGTGTGTAGGG at 343.
  9. AhRYr8: 1, GCGTGGAAAAAG at 310.
  10. AhRYr9: 0.
  11. AhRYr0ci: 1, CTTTTTTCACGC at 661.
  12. AhRYr1ci: 0.
  13. AhRYr2ci: 1, CCCAATGCACGC at 1467.
  14. AhRYr3ci: 1, GGGTAAACACGC at 1818.
  15. AhRYr4ci: 0.
  16. AhRYr5ci: 2, CCGCTTGCACGC at 3471, GGCCACGCACGC at 77.
  17. AhRYr6ci: 0.
  18. AhRYr7ci: 0.
  19. AhRYr8ci: 0.
  20. AhRYr9ci: 1, CCAATGTCACGC at 3436.

AhRYr arbitrary (evens) (4560-2846) UTRs

  1. AhRYr4: GCGTGGGTAAAG at 3739.

AhRYr alternate (odds) (4560-2846) UTRs

  1. AhRYr5: GCGTGATTCGCC at 4380.
  2. AhRYr5ci: CCGCTTGCACGC at 3471.
  3. AhRYr9ci: CCAATGTCACGC at 3436.

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

  1. AhRYr5: GCGTGATTCGCC at 4380.

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

  1. AhRYr2: GCGTGATTTCCG at 1248.
  2. AhRYr4: GCGTGGCTTCTG at 964.
  3. AhRYr6: GCGTGTCATGTG at 1342.
  4. AhRYr8: GCGTGGAAAAAG at 310.
  5. AhRYr0ci: CTTTTTTCACGC at 661.
  6. AhRYr2ci: CCCAATGCACGC at 1467.

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

  1. AhRYr7: GCGTGTGTAGGG at 343.
  2. AhRYr3ci: GGGTAAACACGC at 1818.
  3. AhRYr5ci: GGCCACGCACGC at 77.

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

  1. AhRYr7: GCGTGTGTAGGG at 343.
  2. AhRYr3ci: GGGTAAACACGC at 1818.
  3. AhRYr5ci: CCGCTTGCACGC at 3471, GGCCACGCACGC at 77.
  4. AhRYr9ci: CCAATGTCACGC at 3436.

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

  1. AhRYr2: GCGTGATTTCCG at 1248.
  2. AhRYr4: GCGTGGGTAAAG at 3739, GCGTGGCTTCTG at 964.
  3. AhRYr6: GCGTGTCATGTG at 1342.
  4. AhRYr8: GCGTGGAAAAAG at 310.
  5. AhRYr0ci: CTTTTTTCACGC at 661.
  6. AhRYr2ci: CCCAATGCACGC at 1467.

AhRY analysis and results

Main article: Complex locus A1BG and ZNF497 § AhRYs

The TCDD*AhR DNA-binding consensus sequence is GCGTGNN(A/T)NNN(C/G).[6]

These AhR DNA-binding consensus sequences occur only in the positive direction, eleven sequences all in the distal promoter: three on the negative strand and eight on the positive strand for an occurrence of 5.5. All of the real occurrences were closer to ZNF497 than to A1BG, suggesting promotion of ZNF497. For all four promoters the occurrence would be 2.75.

The random datasets had thirteen sequences in twenty strands for an occurrence of 0.65 per strand independent of direction. One sequence occurred in the arbitrarily chosen negative direction in the UTR out of ten for 0.1, likewise for the core promoter in the positive direction for 0.1. For the distal promoters there were six in the negative direction and five in the positive for occurrences of 0.6 and 0.5 or 0.55.

The unusual distribution of of AhRY elements suggests likely active or activable even if not for A1BG.

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 0 2 0 0
Randoms UTR arbitrary negative 1 10 0.1 0.2
Randoms UTR alternate negative 3 10 0.3 0.2
Reals Core negative 0 2 0 0
Randoms Core arbitrary negative 0 10 0 0
Randoms Core alternate negative 0 10 0 0
Reals Core positive 0 2 0 0
Randoms Core arbitrary positive 1 10 0.1 0.05
Randoms Core alternate positive 0 10 0 0.05
Reals Proximal negative 0 2 0 0
Randoms Proximal arbitrary negative 0 10 0 0
Randoms Proximal alternate negative 0 10 0 0
Reals Proximal positive 0 2 0 0
Randoms Proximal arbitrary positive 0 10 0 0
Randoms Proximal alternate positive 0 10 0 0
Reals Distal negative 0 2 0 0
Randoms Distal arbitrary negative 6 10 0.6 0.45
Randoms Distal alternate negative 3 10 0.3 0.45
Reals Distal positive 11 2 5.5 5.5 ± 2.5 (-+3,++8)
Randoms Distal arbitrary positive 5 10 0.5 0.6
Randoms Distal alternate positive 7 10 0.7 0.6

Comparison:

The occurrences of real AhRY positive direction distals are greater than the randoms. This suggests that the real AhRYs are likely active or activable.

See also

References

  1. ↑ Shen ES, Whitlock JP (April 1992). "Protein-DNA interactions at a dioxin-responsive enhancer. Mutational analysis of the DNA-binding site for the liganded Ah receptor". The Journal of Biological Chemistry. 267 (10): 6815–9. PMID 1313023.
  2. ↑ Wharton KA, Franks RG, Kasai Y, Crews ST (December 1994). "Control of CNS midline transcription by asymmetric E-box-like elements: similarity to xenobiotic responsive regulation". Development. 120 (12): 3563–9. PMID 7821222.
  3. ↑ Bacsi SG, Reisz-Porszasz S, Hankinson O (March 1995). "Orientation of the heterodimeric aryl hydrocarbon (dioxin) receptor complex on its asymmetric DNA recognition sequence". Molecular Pharmacology. 47 (3): 432–8. PMID 7700240.
  4. ↑ Swanson HI, Chan WK, Bradfield CA (November 1995). "DNA binding specificities and pairing rules of the Ah receptor, ARNT, and SIM proteins". The Journal of Biological Chemistry. 270 (44): 26292–302. doi:10.1074/jbc.270.44.26292. PMID 7592839.
  5. ↑ Lusska A, Shen E, Whitlock JP (March 1993). "Protein-DNA interactions at a dioxin-responsive enhancer. Analysis of six bona fide DNA-binding sites for the liganded Ah receptor". The Journal of Biological Chemistry. 268 (9): 6575–80. PMID 8384216.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 Yao EF, Denison MS (June 1992). "DNA sequence determinants for binding of transformed Ah receptor to a dioxin-responsive enhancer". Biochemistry. 31 (21): 5060–7. doi:10.1021/bi00136a019. PMID 1318077.
  7. ↑ Marija Pinne and Judy L. Raucy (10 July 2021). Cytochrome P450 Gene Regulation: Reporter Assays to Assess Aryl Hydrocarbon Receptor (HLHE76, AhR) Activation and Antagonism, In: Cytochrome P450. Methods in Pharmacology and Toxicology. New York, NY USA: Humana. pp. 157–174. doi:10.1007/978-1-0716-1542-3_10. Retrieved 1 November 2021. Text "Template:Isbn " ignored (help)
  8. ↑ 8.0 8.1 Mahmoud Mohamed Mokhtar, Emad Gamil Khidr, Hesham Mohamed Shaban, Shady Allam, Bakheet E. M. Elsadek, Salama Abdou Salama & Shawkey Saddik Ali (28 February 2020). "The effect of aryl hydrocarbon receptor ligands on gentamicin-induced nephrotoxicity in rats". Environmental Science and Pollution Research. 27 (May): 16189–16202. doi:10.1007/s11356-020-08073-z. Retrieved 16 February 2021.
  9. ↑ Nathaniel G. Girer, Dwayne Carter, Nisha Bhattarai, Mehnaz Mustafa, Larry Denner, Craig Porter and Cornelis J. Elferink (22 February 2019). "Inducible loss of the aryl hydrocarbon receptor activates perigonadal white fat respiration and brown fat thermogenesis via fibroblast growth factor 21". International Journal of Molecular Sciences. 20 (4): 950. doi:10.3390/ijms20040950. |access-date= requires |url= (help)
  10. ↑ RefSeq (September 2015). "AHR aryl hydrocarbon receptor [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 5 November 2021.
  11. ↑ 11.0 11.1 L Sadeghi-Amiri, A Barzegar, N Nikbakhsh-Zati, P Mehraban (15 February 2021). "Hypomethylation of the XRE -1383 site is associated with the upregulation of CYP1A1 in gastric adenocarcinoma". Gene. 769 (145216). doi:10.1016/j.gene.2020.145216. PMID 33069801 Check |pmid= value (help). Retrieved 5 November 2021.
  12. ↑ 12.0 12.1 Petra Hudler, Nina Kocevar, and Radovan Komel (14 January 2014). "Proteomic Approaches in Biomarker Discovery: New Perspectives in Cancer Diagnostics". The Scientific Work Journal. 2014 (260348): 18. doi:10.1155/2014/260348. Retrieved 5 November 2021.

External links


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