Xenobiotic responsive 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] within the consensus sequence 5'-T/GNGCGTGA/CG/CA-3'[2][3] in the promoter region of AhR responsive genes. 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'.[4][5][6] Recent research suggests that a second type of element termed AHRE-II, CATG(N6)C[T/A]TG, is capable of indirectly acting with the AhR/ARNT complex.[7][8]

Human genes

Main article: Human genes

Gene ID: 196 is AHR aryl hydrocarbon receptor on 7p21.1.[9] "The protein encoded by this gene is a ligand-activated helix-loop-helix transcription factor involved in the regulation of biological responses to planar aromatic hydrocarbons. This receptor has been shown to regulate xenobiotic-metabolizing enzymes such as cytochrome P450. Before ligand binding, the encoded protein is sequestered in the cytoplasm; upon ligand binding, this protein moves to the nucleus and stimulates transcription of target genes."[9]

Gene expressions

Main article: Gene expressions

Interactions

Main article: Interaction gene transcriptions

Consensus sequences

Main article: Consensus sequence gene transcriptions

(G/T)NGCGTG(A/C)(C/G)A is the consensus sequence for AHRE, DRE or XRE.[2][3]

CATGN6C(A/T)TG is the consensus sequence for AHRE-II.[7][8]

Binding site for

Promoter occurrences

Hypotheses

Main article: Hypotheses
  1. A1BG has no regulatory elements in either promoter.
  2. A1BG is not transcribed by a regulatory element.
  3. No regulatory element participates in the transcription of A1BG.

AHRE-II samplings

Main article: Model samplings

Copying a responsive elements consensus sequence CATGN6C(A/T)TG 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 CATGN6C(A/T)TG (starting with SuccessablesAHREII.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 CATGN6C(A/T)TG, 0.
  2. positive strand, negative direction, looking for CATGN6C(A/T)TG, 1, CATGGTGGCTCATG at 4116.
  3. positive strand, positive direction, looking for CATGN6C(A/T)TG, 0.
  4. negative strand, positive direction, looking for CATGN6C(A/T)TG, 0.
  5. complement, negative strand, negative direction, looking for GTACN6G(A/T)AC, 1, GTACCACCGAGTAC at 4116.
  6. complement, positive strand, negative direction, looking for GTACN6G(A/T)AC, 0.
  7. complement, positive strand, positive direction, looking for GTACN6G(A/T)AC, 0.
  8. complement, negative strand, positive direction, looking for GTACN6G(A/T)AC, 0.
  9. inverse complement, negative strand, negative direction, looking for CA(A/T)GN6CATG, 0.
  10. inverse complement, positive strand, negative direction, looking for CA(A/T)GN6CATG, 1, CATGGTGGCTCATG at 4116.
  11. inverse complement, positive strand, positive direction, looking for CA(A/T)GN6CATG, 0.
  12. inverse complement, negative strand, positive direction, looking for CA(A/T)GN6CATG, 0.
  13. inverse negative strand, negative direction, looking for GT(A/T)CN6GTAC, 1, GTACCACCGAGTAC at 4116.
  14. inverse positive strand, negative direction, looking for GT(A/T)CN6GTAC, 0.
  15. inverse positive strand, positive direction, looking for GT(A/T)CN6GTAC, 0.
  16. inverse negative strand, positive direction, looking for GT(A/T)CN6GTAC, 0.

AHREII UTRs

Main article: UTR promoter gene transcriptions

Positive strand, negative direction: CATGGTGGCTCATG at 4116.

AHRE-II random dataset samplings

  1. AHRE-IIr0: 0.
  2. AHRE-IIr1: 0.
  3. AHRE-IIr2: 0.
  4. AHRE-IIr3: 0.
  5. AHRE-IIr4: 0.
  6. AHRE-IIr5: 0.
  7. AHRE-IIr6: 0.
  8. AHRE-IIr7: 0.
  9. AHRE-IIr8: 0.
  10. AHRE-IIr9: 0.
  11. AHRE-IIr0ci: 0.
  12. AHRE-IIr1ci: 0.
  13. AHRE-IIr2ci: 0.
  14. AHRE-IIr3ci: 0.
  15. AHRE-IIr4ci: 0.
  16. AHRE-IIr5ci: 0.
  17. AHRE-IIr6ci: 0.
  18. AHRE-IIr7ci: 0.
  19. AHRE-IIr8ci: 0.
  20. AHRE-IIr9ci: 0.

AHRE-II analysis and results

Main article: Complex locus A1BG and ZNF497 § AHRE-IIs

CATGN6C(A/T)TG is the consensus sequence for AHRE-II.[7][8]

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 1 2 0.5 0.5
Randoms UTR arbitrary negative 0 10 0 0
Randoms UTR alternate negative 0 10 0 0
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
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 0 10 0 0
Randoms Distal alternate negative 0 10 0 0
Reals Distal positive 0 2 0 0
Randoms Distal arbitrary positive 0 10 0 0
Randoms Distal alternate positive 0 10 0 0

Comparison:

Between ZSCAN22 and A1BG (negative direction) on the positive strand is the consensus sequence CATGGTGGCTCATG at 4116. For four strands (2) and directions (2) there is only only occurrence for 0.25. Using twenty random datasets (ten for the direct and ten for the complement inverse), no consensus sequence for AHRE-II was found for an occurrence of 0.0. This suggests that the one occurrence is not random but likely active or activable.

The occurrences of real AHRE-II is greater than the randoms. This suggests that the real AHRE-II is likely active or activable.

Acknowledgements

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

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. ↑ 2.0 2.1 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.
  3. ↑ 3.0 3.1 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 7.0 7.1 7.2 Boutros PC, Moffat ID, Franc MA, Tijet N, Tuomisto J, Pohjanvirta R, Okey AB (August 2004). "Dioxin-responsive AHRE-II gene battery: identification by phylogenetic footprinting". Biochemical and Biophysical Research Communications. 321 (3): 707–15. doi:10.1016/j.bbrc.2004.06.177. PMID 15358164.
  8. ↑ 8.0 8.1 8.2 Sogawa K, Numayama-Tsuruta K, Takahashi T, Matsushita N, Miura C, Nikawa J, Gotoh O, Kikuchi Y, Fujii-Kuriyama Y (June 2004). "A novel induction mechanism of the rat CYP1A2 gene mediated by Ah receptor-Arnt heterodimer". Biochemical and Biophysical Research Communications. 318 (3): 746–55. doi:10.1016/j.bbrc.2004.04.090. PMID 15144902.
  9. ↑ 9.0 9.1 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 28 October 2021.

External links

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