Copper response element gene transcriptions

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

"Chlamydomonas reinhardtii activates the transcription of the Cyc6 and the Cpx1 genes (encoding cytochrome c6 and coprogen oxidase) in response to copper deficiency."[1]

Human genes

Main article: Human genes

Gene expressions

Main article: Gene expressions

"Mac1p-dependent adaptation to copper deficiency involves the coordinate expression of genes, CTR1, CTR3, FRE1, and FRE7, encoding assimilatory components, through copper-response elements associated with each of these genes (10., 11., 12.)."[1]

The "Cyc6 gene contains at least two copper-response elements (CuREs) (28)."[1]

Interactions

Main article: Interaction gene transcriptions

Consensus sequences

Main article: Consensus sequence gene transcriptions

"A consensus copper-response element [CuRE] TTTGC(T/G)C(A/G) (12) is a binding site for Mac1p."[1]

"An additional EMSA result demonstrated that [Aspergillus fumigatus (Af)] AfMac1 directly binds to a copper response element in the promoter regions of the ctrA2 and ctrC genes with a defined consensus DNA motif (5′-TGTGCTCA-3′) (Park et al., 2017[2]), which is strikingly similar to the Mac1-binding motif in S. cerevisiae (Jamison McDaniels et al., 1999; Keller et al., 2000), suggesting that the mechanism of Mac1-mediated copper homeostasis may be conserved across fungal species."[3]

Binding site for

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.

CuRE (Quinn) samplings

Main article: Model samplings

Copying a responsive elements consensus sequence TTTGC(G/T)C(A/G) 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 TTTGC(G/T)C(A/G) (starting with SuccessablesCuRE.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 TTTGC(G/T)C(A/G), 0.
  2. positive strand, negative direction, looking for TTTGC(G/T)C(A/G), 0.
  3. positive strand, positive direction, looking for TTTGC(G/T)C(A/G), 0.
  4. negative strand, positive direction, looking for TTTGC(G/T)C(A/G), 0.
  5. complement, negative strand, negative direction, looking for AAACG(A/C)G(C/T), 0.
  6. complement, positive strand, negative direction, looking for AAACG(A/C)G(C/T), 0.
  7. complement, positive strand, positive direction, looking for AAACG(A/C)G(C/T), 0.
  8. complement, negative strand, positive direction, looking for AAACG(A/C)G(C/T), 0.
  9. inverse complement, negative strand, negative direction, looking for (C/T)G(A/C)GCAAA, 0.
  10. inverse complement, positive strand, negative direction, looking for (C/T)G(A/C)GCAAA, 1, CGCGCAAA at 163.
  11. inverse complement, positive strand, positive direction, looking for (C/T)G(A/C)GCAAA, 0.
  12. inverse complement, negative strand, positive direction, looking for (C/T)G(A/C)GCAAA, 0.
  13. inverse negative strand, negative direction, looking for (A/G)C(G/T)CGTTT, 1, GCGCGTTT at 163.
  14. inverse positive strand, negative direction, looking for (A/G)C(G/T)CGTTT, 0.
  15. inverse positive strand, positive direction, looking for (A/G)C(G/T)CGTTT, 0.
  16. inverse negative strand, positive direction, looking for (A/G)C(G/T)CGTTT, 0.

CuRE (Quinn) negative direction (2596-1) distal promoters

  1. Positive strand, negative direction: CGCGCAAA at 163.

CuRE (Quinn) random dataset samplings

  1. CuREQr0: 0.
  2. CuREQr1: 0.
  3. CuREQr2: 0.
  4. CuREQr3: 0.
  5. CuREQr4: 0.
  6. CuREQr5: 0.
  7. CuREQr6: 0.
  8. CuREQr7: 0.
  9. CuREQr8: 0.
  10. CuREQr9: 0.
  11. CuREQr0ci: 0.
  12. CuREQr1ci: 0.
  13. CuREQr2ci: 1, CGAGCAAA at 2440.
  14. CuREQr3ci: 0.
  15. CuREQr4ci: 0.
  16. CuREQr5ci: 0.
  17. CuREQr6ci: 2, TGAGCAAA at 3845, TGCGCAAA at 361.
  18. CuREQr7ci: 0.
  19. CuREQr8ci: 0.
  20. CuREQr9ci: 0.

CuREQr arbitrary (evens) (4560-2846) UTRs

  1. CuREQr6ci: TGAGCAAA at 3845.

CuRE (Quinn)r arbitrary negative direction (evens) (2596-1) distal promoters

  1. CuREQr2ci: CGAGCAAA at 2440.
  2. CuREQr6ci: TGCGCAAA at 361.

CuRE (Quinn)r alternate positive direction (evens) (4050-1) distal promoters

  1. CuREQr2ci: CGAGCAAA at 2440.
  2. CuREQr6ci: TGAGCAAA at 3845, TGCGCAAA at 361.

CuRE (Quinn) analysis and results

Main article: Complex locus A1BG and ZNF497 § CuREQs

"A consensus copper-response element [CuRE] TTTGC(T/G)C(A/G) (12) is a binding site for Mac1p."[1]

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 0.05
Randoms UTR alternate negative 0 10 0 0.05
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 1 2 0.5 0.5 ± 0.5 (--0,+-1)
Randoms Distal arbitrary negative 2 10 0.2 0.1
Randoms Distal alternate negative 0 10 0 0.1
Reals Distal positive 0 2 0 0
Randoms Distal arbitrary positive 0 10 0 0.15
Randoms Distal alternate positive 3 10 0.3 0.15

Comparison:

The occurrences of real CuRE (Quinn)s are greater than the randoms. This suggests that the real CuRE (Quinn)s are likely active or activable.

CuRE (Park) samplings

Copying a responsive elements consensus sequence TGTGCTCA 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 TGTGCTCA (starting with SuccessablesPark.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 TGTGCTCA, 0.
  2. positive strand, negative direction, looking for TGTGCTCA, 0.
  3. positive strand, positive direction, looking for TGTGCTCA, 0.
  4. negative strand, positive direction, looking for TGTGCTCA, 0.
  5. complement, negative strand, negative direction, looking for ACACGAGT, 0.
  6. complement, positive strand, negative direction, looking for ACACGAGT, 0.
  7. complement, positive strand, positive direction, looking for ACACGAGT, 0.
  8. complement, negative strand, positive direction, looking for ACACGAGT, 0.
  9. inverse complement, negative strand, negative direction, looking for TGAGCACA, 0.
  10. inverse complement, positive strand, negative direction, looking for TGAGCACA, 0.
  11. inverse complement, positive strand, positive direction, looking for TGAGCACA, 0.
  12. inverse complement, negative strand, positive direction, looking for TGAGCACA, 1, TGAGCACA at 3740.
  13. inverse negative strand, negative direction, looking for ACTCGTGT, 0.
  14. inverse positive strand, negative direction, looking for ACTCGTGT, 0.
  15. inverse positive strand, positive direction, looking for ACTCGTGT, 1, ACTCGTGT at 3740.
  16. inverse negative strand, positive direction, looking for ACTCGTGT, 0.

CuRE(Park) positive direction (4050-1) distal promoters

  1. Negative strand, positive direction: TGAGCACA at 3740.

CuRE (Park) random dataset samplings

  1. CuREPr0: 0.
  2. CuREPr1: 0.
  3. CuREPr2: 0.
  4. CuREPr3: 0.
  5. CuREPr4: 0.
  6. CuREPr5: 0.
  7. CuREPr6: 0.
  8. CuREPr7: 0.
  9. CuREPr8: 0.
  10. CuREPr9: 0.
  11. CuREPr0ci: 0.
  12. CuREPr1ci: 1, TGAGCACA at 2259.
  13. CuREPr2ci: 0.
  14. CuREPr3ci: 0.
  15. CuREPr4ci: 0.
  16. CuREPr5ci: 0.
  17. CuREPr6ci: 0.
  18. CuREPr7ci: 0.
  19. CuREPr8ci: 0.
  20. CuREPr9ci: 0.

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

  1. CuREPr1ci: TGAGCACA at 2259.

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

  1. CuREPr1ci: TGAGCACA at 2259.

Copper response element analyses and results

Main article: Complex locus A1BG and ZNF497 § CuREPs

"An additional EMSA result demonstrated that [Aspergillus fumigatus (Af)] AfMac1 directly binds to a copper response element in the promoter regions of the ctrA2 and ctrC genes with a defined consensus DNA motif (5′-TGTGCTCA-3′) (Park et al., 2017[2]), which is strikingly similar to the Mac1-binding motif in S. cerevisiae (Jamison McDaniels et al., 1999; Keller et al., 2000), suggesting that the mechanism of Mac1-mediated copper homeostasis may be conserved across fungal species."[3]

The consensus sequence for the copper response element (Park 2017): TGTGCTCA, only occurs as an inverse complement TGAGCACA at 3740 on the negative strand in the positive direction in the distal promoter closer to A1BG than ZNF497. This inverse complement has an occurrence of 0.5.

The randoms also have only one occurrence, an inverse complement TGAGCACA at 2259 in the arbitrary positive direction. This inverse complement had an occurrence of 0.1. The difference in occurrences between real and random suggests that the real TGAGCACA at 3740 is likely active or activable.

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 0 2 0 0
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 0.05
Randoms Distal alternate negative 1 10 0.1 0.05
Reals Distal positive 1 2 0.5 0.5 ± 0.5 (-+1,++0)
Randoms Distal arbitrary positive 1 10 0.1 0.05
Randoms Distal alternate positive 0 10 0 0.05

Comparison:

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

Acknowledgements

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

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Jeanette M. Quinn, Paola Barraco, Mats Eriksson and Sabeeha Merchant (March 2000). "Coordinate Copper- and Oxygen-responsive Cyc6 and Cpx1 Expression in Chlamydomonas Is Mediated by the Same Element". Journal of Biological Chemistry. 275 (9): 6080–6089. doi:10.1074/jbc.275.9.6080. Retrieved 1 April 2021.
  2. ↑ 2.0 2.1 Yong-Sung Park, Tae-Hyoung Kim and Cheol-Won Yun (3 July 2017). "Functional characterization of the copper transcription factor AfMac1 from Aspergillus fumigatus". Biochemical Journal. 474 (14): 2365–2378. doi:10.1042/BCJ20170191. Retrieved 2 April 2021.
  3. ↑ 3.0 3.1 Jinxing Song, Rongpeng Li and Jihong Jiang (12 April 2019). "Copper Homeostasis in Aspergillus fumigatus: Opportunities for Therapeutic Development". Frontiers in Microbiology. 10: 774. doi:10.3389/fmicb.2019.00774. Retrieved 2 April 2021.

External links

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