Metal responsive element gene transcriptions

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Editor-In-Chief: Henry A. Hoff

Metal responsive elements (MRE)s, or TGC boxes, may occur in the core promoter of some human DNA genes.

TGC boxes

Notation: let the symbol MT stand for metallothionein.

"The metallothionein (MT) genes provide a good example of eucaryotic promoter architecture. MT genes specify the synthesis of low-molecular-weight metal-binding proteins. They are transcriptionally regulated by the metal ions cadmium and zinc (11), glucocorticoid hormones (18), interferon (14), interleukin-1 (22), and tumor promoters (2). The metal ion regulation of MTs is conferred by a short sequence element called the metal-responsive element (MRE [21]) or TGC box (31, 34), which functions as a metal ion-dependent enhancer."[1]

Consensus sequences

Main article: Consensus sequences

"The promoter regulatory sequences are identified by homology to published GRE (21), MRE (35), and GC box (15) consensus sequences."[1]

Here "is a consensus sequence for the MREs of the rat MT-1 gene."[1] In the direction of transcription on the DNA template strand: 3'-CNNTGCRCYCGGGNC-5', where R = purine; Y = pyrimidine; and N = any nucleotide (nt).[1]

"[T]hree potential metal response elements (MREs) [overlap] the E-boxes in the repeats, (TGCACGT with TGCRCNC being the consensus sequence; 17,18)."[2]

The reproducible consensus sequence seems to be 3'-TGCRCNC-5', specifically 3'-TGC(A/G)CNC-5'.

"To execute the transcriptional regulation, [Metal-responsive transcription factor-1] MTF-1 binds to the specific site, called [metal responsive element] MRE (core sequence = TGCRCNC), in the promoter region of target gene (Günther et al. 2012a)."[3]

MREs

Six MREs lie in the proximal promoter of the rat MT-1 gene upstream of the TATA box to almost -200 nts from the transcription start site.[1]

Hypotheses

Main article: Hypotheses
  1. A1BG has no MREs in either promoter.
  2. A1BG is not transcribed by an MRE.
  3. MREs do not participate in the transcription of A1BG.

MRE samplings

Main articles: Model samplings and Samplings

Copying a responsive elements consensus sequence TGCGCCC 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 (starting with SuccessablesMRE.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 (+), including extending the number of nts from 958 to 4445, the programs are, are looking for, and found:

  1. Negative strand, negative direction: 0.
  2. Negative strand, positive direction: 11, TGCACCC at 3323, TGCACAC at 2963, TGCGCCC at 1657, TGCGCCC at 1499, TGCACTC at 1473, TGCGCCC at 1399, TGCACTC at 1373, TGCGCCC at 1247, TGCACAC at 1221, TGCACAC at 549, TGCGCCC at 453.
  3. Positive strand, negative direction: 7, TGCACTC at 4341, TGCACTC at 3290, TGCACCC at 2762, TGCACTC at 2427, TGCACTC at 2001, TGCACTC at 1348, TGCGCTC at 891.
  4. Positive strand, positive direction: 2, TGCGCCC at 972, TGCGCCC at 872.
  5. inverse complement, negative strand, negative direction: 2, GAGTGCA at 1772, GTGTGCA at 531.
  6. inverse complement, negative strand, positive direction: 10, GGGTGCA at 3883, GGGTGCA at 2800, GAGTGCA at 2326, GAGTGCA at 1786, GTGCGCA at 1523, GCGTGCA at 1218, GGGCGCA at 976, GGGCGCA at 876, GCGCGCA at 684, GCGTGCA at 546.
  7. inverse complement, positive strand, negative direction: 2, GTGTGCA at 2863, GAGTGCA at 1470.
  8. inverse complement, positive strand, positive direction: 0.

MRE (4560-2846) UTRs

  1. Positive strand, negative direction: TGCACTC at 4341, TGCACTC at 3290, GTGTGCA at 2863.

MRE negative direction (2811-2596) proximal promoters

  1. Positive strand, negative direction: TGCACCC at 2762.

MRE negative direction (2596-1) distal promoters

  1. Negative strand, negative direction: GAGTGCA at 1772, GTGTGCA at 531.
  2. Positive strand, negative direction: TGCACTC at 2427, TGCACTC at 2001, GAGTGCA at 1470, TGCACTC at 1348, TGCGCTC at 891.

MRE positive direction (4050-1) distal promoters

  1. Negative strand, positive direction: GGGTGCA at 3883, TGCACCC at 3323, TGCACAC at 2963, GGGTGCA at 2800, GAGTGCA at 2326, GAGTGCA at 1786, TGCGCCC at 1657, GTGCGCA at 1523, TGCGCCC at 1499, TGCACTC at 1473, TGCGCCC at 1399, TGCACTC at 1373, TGCGCCC at 1247, TGCACAC at 1221, GCGTGCA at 1218, GGGCGCA at 976, GGGCGCA at 876, GCGCGCA at 684, TGCACAC at 549, GCGTGCA at 546, TGCGCCC at 453.
  2. Positive strand, positive direction: TGCGCCC at 972, TGCGCCC at 872.

MRE random dataset samplings

  1. MREr0: 1, TGCGCGC at 3885.
  2. MREr1: 0.
  3. MREr2: 2, TGCACGC at 1467, TGCGCCC at 707.
  4. MREr3: 1, TGCGCTC at 2481.
  5. MREr4: 3, TGCACTC at 3066, TGCACAC at 2198, TGCACCC at 914.
  6. MREr5: 4, TGCGCCC at 3547, TGCACGC at 3471, TGCGCTC at 2006, TGCGCCC at 702.
  7. MREr6: 2, TGCGCCC at 3314, TGCGCGC at 2071.
  8. MREr7: 3, TGCACTC at 3480, TGCACCC at 2906, TGCACCC at 1986.
  9. MREr8: 0.
  10. MREr9: 3, TGCACAC at 4032, TGCACCC at 2744, TGCACAC at 2712.
  11. MREr0ci: 1, GGGTGCA at 1400.
  12. MREr1ci: 0.
  13. MREr2ci: 0.
  14. MREr3ci: 2, GGGTGCA at 4128, GGGCGCA at 2166.
  15. MREr4ci: 1, GGGCGCA at 1628.
  16. MREr5ci: 1, GAGTGCA at 818.
  17. MREr6ci: 1, GGGCGCA at 3374.
  18. MREr7ci: 3, GGGTGCA at 3768, GGGTGCA at 2580, GTGTGCA at 1681.
  19. MREr8ci: 1, GGGCGCA at 1694.
  20. MREr9ci: 0.

MREr arbitrary (evens) (4560-2846) UTRs

  1. MREr0: TGCGCGC at 3885.
  2. MREr4: TGCACTC at 3066.
  3. MREr6: TGCGCCC at 3314.
  4. MREr6ci: GGGCGCA at 3374.

MREr alternate (odds) (4560-2846) UTRs

  1. MREr7: TGCACTC at 3480, TGCACCC at 2906.
  2. MREr9: TGCACAC at 4032.
  3. MREr7ci: GGGTGCA at 3768.

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

  1. MREr9: TGCACCC at 2744, TGCACAC at 2712.

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

  1. MREr2: TGCACGC at 1467, TGCGCCC at 707.
  2. MREr4: TGCACAC at 2198, TGCACCC at 914.
  3. MREr6: TGCGCGC at 2071.
  4. MREr4ci: GGGCGCA at 1628.
  5. MREr8ci: GGGCGCA at 1694.

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

  1. MREr3: TGCGCTC at 2481.
  2. MREr7: TGCACCC at 1986.
  3. MREr5ci: GAGTGCA at 818.
  4. MREr7ci: GGGTGCA at 2580, GTGTGCA at 1681.

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

  1. MREr3: TGCGCTC at 2481.
  2. MREr7: TGCACTC at 3480, TGCACCC at 2906, TGCACCC at 1986.
  3. MREr9: TGCACAC at 4032, TGCACCC at 2744, TGCACAC at 2712.
  4. MREr5ci: GAGTGCA at 818.
  5. MREr7ci: GGGTGCA at 3768, GGGTGCA at 2580, GTGTGCA at 1681.

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

  1. MREr0: TGCGCGC at 3885.
  2. MREr2: TGCACGC at 1467, TGCGCCC at 707.
  3. MREr4: TGCACTC at 3066, TGCACAC at 2198, TGCACCC at 914.
  4. MREr6: TGCGCCC at 3314, TGCGCGC at 2071.
  5. MREr4ci: GGGCGCA at 1628.
  6. MREr6ci: GGGCGCA at 3374.
  7. MREr8ci: GGGCGCA at 1694.

MRE analysis and results

Main article: Complex locus A1BG and ZNF497 § MREs

"To execute the transcriptional regulation, [Metal-responsive transcription factor-1] MTF-1 binds to the specific site, called [metal responsive element] MRE (core sequence = TGCRCNC), in the promoter region of target gene (Günther et al. 2012a)."[3] TGCRCNC = TGC(A/G)CNC so ci is GNG(C/T)GCA.

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 3 2 1.5 1.5 ± 0.5 (--0,+-3)
Randoms UTR arbitrary negative 4 10 0.4 0.4
Randoms UTR alternate negative 4 10 0.4 0.4
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 1 2 0.5 0.5 ± 0.5 (--0,+-1)
Randoms Proximal arbitrary negative 0 10 0 0.1
Randoms Proximal alternate negative 2 10 0.2 0.1
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 7 2 3.5 3.5 ± 1.5 (--2,+-5)
Randoms Distal arbitrary negative 7 10 0.7 0.6
Randoms Distal alternate negative 5 10 0.5 0.6
Reals Distal positive 23 2 11.5 11.5 ± 9.5 (-+21,++2)
Randoms Distal arbitrary positive 11 10 1.1 1.1
Randoms Distal alternate positive 11 10 1.1 1.1

Comparison:

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

Acknowledgements

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

Initial content for this page in some instances came from Wikiversity.

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Robert D. Andersen, Susan J. Taplitz, Sandy Wong, Greg Bristol, Bill Larkin, and Harvey R. Herschman (1987). "Metal-Dependent Binding of a Factor In Vivo to the Metal-Responsive Elements of the Metallothionein 1 Gene Promoter". Molecular and Cellular Biology. 7 (10): 3574–81. doi:10.1128/​MCB.7.10.3574 Check |doi= value (help). Retrieved 2013-04-15. Unknown parameter |month= ignored (help); Unknown parameter |pdf= ignored (help); zero width space character in |doi= at position 9 (help)
  2. ↑ Barbara Levinson, Rebecca Conant, Rhonda Schnur, Soma Das, Seymour Packman and Jane Gitschier (1996). "A Repeated Element in the Regulatory Region of the MNK Gene and Its Deletion in A Patient With Occipital Horn Syndrome". Human Molecular Genetics. 5 (11): 1737–42. doi:10.1093/hmg/5.11.1737. Retrieved 2013-04-15.
  3. ↑ 3.0 3.1 Sang Yoon Lee & Yoon Kwon Nam (3 July 2017). "Molecular cloning of metal-responsive transcription factor-1 (MTF-1) and transcriptional responses to metal and heat stresses in Pacific abalone, Haliotis discus hannai". Fisheries and Aquatic Sciences. 20: 9. doi:10.1186/s41240-017-0055-y. Retrieved 16 October 2020.

Further reading

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