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

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 AAAAAAAA (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 AAAAAAAA, 0.
  2. positive strand, negative direction, looking for AAAAAAAA, 0.
  3. positive strand, positive direction, looking for AAAAAAAA, 0.
  4. negative strand, positive direction, looking for AAAAAAAA, 0.
  5. complement, negative strand, negative direction, looking for TTTTTTTT, 0.
  6. complement, positive strand, negative direction, looking for TTTTTTTT, 0.
  7. complement, positive strand, positive direction, looking for TTTTTTTT, 0.
  8. complement, negative strand, positive direction, looking for TTTTTTTT, 0.
  9. inverse complement, negative strand, negative direction, looking for TTTTTTTT, 0.
  10. inverse complement, positive strand, negative direction, looking for TTTTTTTT, 0.
  11. inverse complement, positive strand, positive direction, looking for TTTTTTTT, 0.
  12. inverse complement, negative strand, positive direction, looking for TTTTTTTT, 0.
  13. inverse negative strand, negative direction, looking for AAAAAAAA, 0.
  14. inverse positive strand, negative direction, looking for AAAAAAAA, 0.
  15. inverse positive strand, positive direction, looking for AAAAAAAA, 0.
  16. inverse negative strand, positive direction, looking for AAAAAAAA, 0.

AAA UTRs

AAA core promoters

AAA proximal promoters

AAA distal promoters

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.

For the Basic programs testing consensus sequence TNGCGTG (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.

DRE UTRs

Positive strand, negative direction: CACGCCA at 3282.

DRE distal promoters

Negative strand, negative direction: CACGCCA at 2198, CACGCCA at 381.

Positive strand, negative direction: CACGCCA at 2209, CACGCCA at 1993.

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

Xenobiotic response element samplings

"The megalin (LRP2) gene promoter region [shows] eight consensus sequence of XRE 5′-GCGTG-3′."[7]

"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."[8]

Copying a responsive elements consensus sequence GCGTG 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 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 AAAAAAAA, 0.
  2. positive strand, negative direction, looking for AAAAAAAA, 0.
  3. positive strand, positive direction, looking for AAAAAAAA, 0.
  4. negative strand, positive direction, looking for AAAAAAAA, 0.
  5. complement, negative strand, negative direction, looking for TTTTTTTT, 0.
  6. complement, positive strand, negative direction, looking for TTTTTTTT, 0.
  7. complement, positive strand, positive direction, looking for TTTTTTTT, 0.
  8. complement, negative strand, positive direction, looking for TTTTTTTT, 0.
  9. inverse complement, negative strand, negative direction, looking for TTTTTTTT, 0.
  10. inverse complement, positive strand, negative direction, looking for TTTTTTTT, 0.
  11. inverse complement, positive strand, positive direction, looking for TTTTTTTT, 0.
  12. inverse complement, negative strand, positive direction, looking for TTTTTTTT, 0.
  13. inverse negative strand, negative direction, looking for AAAAAAAA, 0.
  14. inverse positive strand, negative direction, looking for AAAAAAAA, 0.
  15. inverse positive strand, positive direction, looking for AAAAAAAA, 0.
  16. inverse negative strand, positive direction, looking for AAAAAAAA, 0.

XRE UTRs

XRE core promoters

XRE proximal promoters

XRE distal promoters

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 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. 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.
  8. 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)

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