P53 response element gene transcriptions

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

"A p53 consensus DNA RE is composed of a tandem of two decameric palindromic sequences (half-sites) 5′-RRRCWWGYYY-3′, where R = purine, Y = pyrimidine and W is either A or T. There is a variability in composition of p53 REs, thus two half-sites can be separated by a spacer DNA, typically 0–13 bp in length and many p53 DNA REs have varying numbers of half-sites (19,20,22,33–37)."[1]

"The p53 REs are defined by two closely spaced decameric half-sites [consensus sequence: 5′-(RRRCWWGYYY)n(RRRCWWGYYY)-3′; R = A,G; W = A,T; Y = C,T; n = spacer of length 0–20 base pairs (bp)], and hundreds of them have been validated in human and mouse (1)."[2]

"According to EMSA binding experiments, all core sequences CAGG and CGTG and their palindrome sequences CCTG and CACG can be bound by p63 [18]. TAACATGTTT or TAACTTGTAT or TAACCTGTAT or TAACGTGTAT bound to p63 much more strongly than AGGCATGATG or GAGCTTGATT or GACCCTGACC or CCCCGTGCAC in EMSA experiments [21]. Therefore, p63 prefers AT-rich flanking sequences rather than general GC rich in purine (Pu) and pyrimidine (Py) bases that comprise the flanking sequence for p53 or p73 [...] [21]."[3]

Human genes

p53 response elements found in the promoter of TUG1: 5'-CAGGCCC-3' and 5'-GGGCGTG-3'.[4]

Consensus sequences

An apparent consensus sequence for the p53RE is (A/G)(A/G)(A/G)C(A/T)(A/T)G(C/T)(C/T)(C/T).

Samplings

Copying an apparent consensus sequence for the p53RE (GGGCATGCCT) and putting it in "⌘F" finds none located between ZSCAN22 and none between ZNF497 and A1BG as can be found by the computer programs.

Copying an apparent core consensus sequence for the p53RE (CAGG) and putting it in "⌘F" finds three located between ZSCAN22 and 49 between ZNF497 and A1BG as can be found by the computer programs.

Copying an apparent core consensus sequence for the p53RE (CGTG) and putting it in "⌘F" finds 27 located between ZSCAN22 and eleven between ZNF497 and A1BG as can be found by the computer programs.

Copying an apparent consensus sequence for the p53RE (TAACATGTTT) and putting it in "⌘F" finds none located between ZSCAN22 and none between ZNF497 and A1BG as can be found by the computer programs.

Copying an apparent consensus sequence for the p53RE (TAACTTGTAT) and putting it in "⌘F" finds none located between ZSCAN22 and none between ZNF497 and A1BG as can be found by the computer programs.

Copying an apparent consensus sequence for the p53RE (TAACCTGTAT) and putting it in "⌘F" finds none located between ZSCAN22 and none between ZNF497 and A1BG as can be found by the computer programs.

Copying an apparent consensus sequence for the p53RE (TAACGTGTAT) and putting it in "⌘F" finds none located between ZSCAN22 and none between ZNF497 and A1BG as can be found by the computer programs.

Copying an apparent consensus sequence for the p53RE (AGGCATGATG) and putting it in "⌘F" finds none located between ZSCAN22 and none between ZNF497 and A1BG as can be found by the computer programs.

Copying an apparent consensus sequence for the p53RE (GAGCTTGATT) and putting it in "⌘F" finds none located between ZSCAN22 and none between ZNF497 and A1BG as can be found by the computer programs.

Copying an apparent consensus sequence for the p53RE (GACCCTGACC) and putting it in "⌘F" finds none located between ZSCAN22 and none between ZNF497 and A1BG as can be found by the computer programs.

Copying an apparent consensus sequence for the p53RE (CCCCGTGCAC) and putting it in "⌘F" finds none located between ZSCAN22 and none between ZNF497 and A1BG as can be found by the computer programs.

For the Basic programs (starting with SuccessablesPbox.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 in the negative direction (from ZSCAN22 to A1BG) is SuccessablesPRE--.bas, looking for 3'-(A/G)(A/G)(A/G)C(A/T)(A/T)G(C/T)(C/T)(C/T)-5', 0.
  2. negative strand in the positive direction (from ZNF497 to A1BG) is SuccessablesPRE-+.bas, looking for 3'-(A/G)(A/G)(A/G)C(A/T)(A/T)G(C/T)(C/T)(C/T)-5', 0.
  3. positive strand in the negative direction is SuccessablesPRE+-.bas, looking for 3'-(A/G)(A/G)(A/G)C(A/T)(A/T)G(C/T)(C/T)(C/T)-5', 3, 3'-AGGCAAGCCT-5', 457, 3'-AGACTTGCCT-5', 1621, 3'-AGACAAGCTT-5', 4186.
  4. positive strand in the positive direction is SuccessablesPRE++.bas, looking for 3'-(A/G)(A/G)(A/G)C(A/T)(A/T)G(C/T)(C/T)(C/T)-5', 0.
  5. complement, negative strand, negative direction is SuccessablesPREc--.bas, looking for 3'-(C/T)(C/T)(C/T)G(A/T)(A/T)C(A/G)(A/G)(A/G)-5', 3, 3'-TCCGTTCGGA-5', 457, 3'-TCTGAACGGA-5', 1621, 3'-TCTGTTCGAA-5', 4186.
  6. complement, negative strand, positive direction is SuccessablesPREc-+.bas, looking for 3'-(C/T)(C/T)(C/T)G(A/T)(A/T)C(A/G)(A/G)(A/G)-5', 0.
  7. complement, positive strand, negative direction is SuccessablesPREc+-.bas, looking for 3'-(C/T)(C/T)(C/T)G(A/T)(A/T)C(A/G)(A/G)(A/G)-5', 0.
  8. complement, positive strand, positive direction is SuccessablesPREc++.bas, looking for 3'-(C/T)(C/T)(C/T)G(A/T)(A/T)C(A/G)(A/G)(A/G)-5', 0.

p53 response element UTRs

Positive strand, negative direction: AGACAAGCTT at 4186.

p53 response element distal promoters

Positive strand, negative direction: AGACTTGCCT at 1621, AGGCAAGCCT at 457.

p53 random dataset samplings

  1. PREr0: 0.
  2. PREr1: 0.
  3. PREr2: 2, AAACTAGCCT at 4165, AGACTTGTTT at 2348.
  4. PREr3: 0.
  5. PREr4: 1, AGGCAAGCTC at 4406.
  6. PREr5: 1, AAACATGTTT at 144.
  7. PREr6: 1, GGGCTTGTCC at 3577.
  8. PREr7: 0.
  9. PREr8: 1, GAACAAGTTT at 3172.
  10. PREr9: 2, GGGCTTGTTT at 3168, AGGCAAGCCC at 1117.

PREr arbitrary (evens) (4560-2846) UTRs

  1. PREr2: AAACTAGCCT at 4165.
  2. PREr4: AGGCAAGCTC at 4406.
  3. PREr6: GGGCTTGTCC at 3577.
  4. PREr8: GAACAAGTTT at 3172.

PREr alternate (odds) (4560-2846) UTRs

  1. PREr9: GGGCTTGTTT at 3168.

PREr alternate positive direction (evens) (4445-4265) core promoters

  1. PREr4: AGGCAAGCTC at 4406.

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

  1. PREr2: AAACTAGCCT at 4165.

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

  1. PREr2: AGACTTGTTT at 2348.

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

  1. PREr5: AAACATGTTT at 144.
  2. PREr9: AGGCAAGCCC at 1117.

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

  1. PREr5: AAACATGTTT at 144.
  2. PREr9: GGGCTTGTTT at 3168, AGGCAAGCCC at 1117.

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

  1. PREr2: AGACTTGTTT at 2348.
  2. PREr6: GGGCTTGTCC at 3577.
  3. PREr8: GAACAAGTTT at 3172.

p53 analysis and results

Main article: Complex locus A1BG and ZNF497 § P53s

"The p53 REs are defined by two closely spaced decameric half-sites [consensus sequence: 5′-(RRRCWWGYYY)n(RRRCWWGYYY)-3′; R = A,G; W = A,T; Y = C,T; n = spacer of length 0–20 base pairs (bp)], and hundreds of them have been validated in human and mouse (1)."[2]

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 4 10 0.4 0.25
Randoms UTR alternate negative 1 10 0.1 0.25
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 0.05
Randoms Core alternate positive 1 10 0.1 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 0.05
Randoms Proximal alternate positive 1 10 0.1 0.05
Reals Distal negative 2 2 1 1 ± 1 (--0,+-2)
Randoms Distal arbitrary negative 1 10 0.1 0.15
Randoms Distal alternate negative 2 10 0.2 0.15
Reals Distal positive 0 2 0 0
Randoms Distal arbitrary positive 3 10 0.3 0.3
Randoms Distal alternate positive 3 10 0.3 0.3

Comparison:

The occurrences of real p53s are greater than the randoms. This suggests that the real p53s are likely active or activable.

p53 (Long1) samplings

Main article: Model samplings

Copying a responsive elements consensus sequence CAGGCCC 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 CAGGCCC (starting with SuccessablesLong1.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 CAGGCCC, 0.
  2. positive strand, negative direction, looking for CAGGCCC, 0.
  3. positive strand, positive direction, looking for CAGGCCC, 0.
  4. negative strand, positive direction, looking for CAGGCCC, 1, CAGGCCC at 93.
  5. complement, negative strand, negative direction, looking for GTCCGGG, 0.
  6. complement, positive strand, negative direction, looking for GTCCGGG, 0.
  7. complement, positive strand, positive direction, looking for GTCCGGG, 1, GTCCGGG at 93.
  8. complement, negative strand, positive direction, looking for GTCCGGG, 0.
  9. inverse complement, negative strand, negative direction, looking for GGGCCTG, 0.
  10. inverse complement, positive strand, negative direction, looking for GGGCCTG, 0.
  11. inverse complement, positive strand, positive direction, looking for GGGCCTG, 1, GGGCCTG at 745.
  12. inverse complement, negative strand, positive direction, looking for GGGCCTG, 1, GGGCCTG at 285.
  13. inverse negative strand, negative direction, looking for CCCGGAC, 0.
  14. inverse positive strand, negative direction, looking for CCCGGAC, 0.
  15. inverse positive strand, positive direction, looking for CCCGGAC, 1, CCCGGAC at 285.
  16. inverse negative strand, positive direction, looking for CCCGGAC, 1, CCCGGAC at 745.

p53 (Long1) distal promoters

Main article: Distal promoter gene transcriptions

Negative strand, positive direction,: GGGCCTG at 285, CAGGCCC at 93.

Positive strand, positive direction: GGGCCTG at 745.

P53 (Long1) random dataset samplings

  1. Long1r0: 1, CAGGCCC at 584.
  2. Long1r1: 1, CAGGCCC at 78.
  3. Long1r2: 1, CAGGCCC at 76.
  4. Long1r3: 0.
  5. Long1r4: 0.
  6. Long1r5: 2, CAGGCCC at 2617, CAGGCCC at 1924.
  7. Long1r6: 1, CAGGCCC at 1402.
  8. Long1r7: 0.
  9. Long1r8: 1, CAGGCCC at 1090.
  10. Long1r9: 0.
  11. Long1r0ci: 0.
  12. Long1r1ci: 1, GGGCCTG at 2388.
  13. Long1r2ci: 0.
  14. Long1r3ci: 0.
  15. Long1r4ci: 0.
  16. Long1r5ci: 0.
  17. Long1r6ci: 0.
  18. Long1r7ci: 0.
  19. Long1r8ci: 0.
  20. Long1r9ci: 0.

Long1r alternate negative direction (odds) (2811-2596) proximal promoters

  1. Long1r5: CAGGCCC at 2617.

Long1r arbitrary negative direction (evens) (2596-1) distal promoters

  1. Long1r0: CAGGCCC at 584.
  2. Long1r2: CAGGCCC at 76.
  3. Long1r6: CAGGCCC at 1402.
  4. Long1r8: CAGGCCC at 1090.

Long1r alternate negative direction (odds) (2596-1) distal promoters

  1. Long1r1: CAGGCCC at 78.
  2. Long1r5: CAGGCCC at 1924.
  3. Long1r1ci: GGGCCTG at 2388.

Long1r arbitrary positive direction (odds) (4050-1) distal promoters

  1. Long1r1: CAGGCCC at 78.
  2. Long1r5: CAGGCCC at 2617, CAGGCCC at 1924.
  3. Long1r1ci: GGGCCTG at 2388.

Long1r alternate positive direction (evens) (4050-1) distal promoters

  1. Long1r0: CAGGCCC at 584.
  2. Long1r2: CAGGCCC at 76.
  3. Long1r6: CAGGCCC at 1402.
  4. Long1r8: CAGGCCC at 1090.

Response element analysis and results

Main article: Complex locus A1BG and ZNF497 § p53 (Long1)s

p53 response element found in the promoter of TUG1: CAGGCCC.[4]

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 0.05
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 0 2 0 0
Randoms Distal arbitrary negative 4 10 0.4 0.35
Randoms Distal alternate negative 3 10 0.3 0.35
Reals Distal positive 3 2 1.5 1.5 ± 0.5 (-+2,++1)
Randoms Distal arbitrary positive 4 10 0.4 0.4
Randoms Distal alternate positive 4 10 0.4 0.4

Comparison:

The occurrences of real p53 (Long1)s are greater than the randoms. This suggests that the real p53 (Long1)s are likely active or activable.

p53 (Long2) samplings

Main article: Model samplings

Copying a responsive elements consensus sequence GGGCGTG 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 GGGCGTG (starting with SuccessablesAAA.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 GGGCGTG, 0.
  2. positive strand, negative direction, looking for GGGCGTG, 3, GGGCGTG at 3046, GGGCGTG at 1896, GGGCGTG at 1243.
  3. positive strand, positive direction, looking for GGGCGTG, 0.
  4. negative strand, positive direction, looking for GGGCGTG, 1, GGGCGTG at 1719.
  5. complement, negative strand, negative direction, looking for CCCGCAC, 3, CCCGCAC at 3046, CCCGCAC at 1896, CCCGCAC at 1243.
  6. complement, positive strand, negative direction, looking for CCCGCAC, 0.
  7. complement, positive strand, positive direction, looking for CCCGCAC, 1, CCCGCAC at 1719.
  8. complement, negative strand, positive direction, looking for CCCGCAC, 0.
  9. inverse complement, negative strand, negative direction, looking for CACGCCC, 0.
  10. inverse complement, positive strand, negative direction, looking for CACGCCC, 0.
  11. inverse complement, positive strand, positive direction, looking for CACGCCC, 3, CACGCCC at 1765, CACGCCC at 1591, CACGCCC at 490.
  12. inverse complement, negative strand, positive direction, looking for CACGCCC, 0.
  13. inverse negative strand, negative direction, looking for GTGCGGG, 0.
  14. inverse positive strand, negative direction, looking for GTGCGGG, 0.
  15. inverse positive strand, positive direction, looking for GTGCGGG, 0.
  16. inverse negative strand, positive direction, looking for GTGCGGG, 3, GTGCGGG at 1765, GTGCGGG at 1591, GTGCGGG at 490.

p53 (Long2) (4560-2846) UTRs

  1. Positive strand, negative direction: GGGCGTG at 3046.

p53 (Long2) negative direction (2596-1) distal promoters

  1. Positive strand, negative direction: GGGCGTG at 1896, GGGCGTG at 1243.

p53 (Long2) positive direction (4050-1) distal promoters

  1. Negative strand, positive direction: GGGCGTG at 1719.
  2. Positive strand, positive direction: CACGCCC at 1765, CACGCCC at 1591, CACGCCC at 490.

p53 (Long2) random dataset samplings

  1. Long2r0: 1, GGGCGTG at 1076.
  2. Long2r1: 0.
  3. Long2r2: 0.
  4. Long2r3: 0.
  5. Long2r4: 1, GGGCGTG at 3732.
  6. Long2r5: 1, GGGCGTG at 4373.
  7. Long2r6: 0.
  8. Long2r7: 2, GGGCGTG at 1789, GGGCGTG at 452.
  9. Long2r8: 0.
  10. Long2r9: 0.
  11. Long2r0ci: 0.
  12. Long2r1ci: 1, CACGCCC at 2665.
  13. Long2r2ci: 0.
  14. Long2r3ci: 0.
  15. Long2r4ci: 0.
  16. Long2r5ci: 0.
  17. Long2r6ci: 1, CACGCCC at 1675.
  18. Long2r7ci: 0.
  19. Long2r8ci: 0.
  20. Long2r9ci: 0.

Long2r arbitrary (evens) (4560-2846) UTRs

  1. Long2r4: GGGCGTG at 3732.

Long2r arbitrary (odds) (4560-2846) UTRs

  1. Long2r5: 1, GGGCGTG at 4373.

Long2r arbitrary positive direction (odds) (4445-4265) core promoters

  1. Long2r5: GGGCGTG at 4373.

Long2r alternate negative direction (odds) (2811-2596) proximal promoters

  1. Long2r1ci: CACGCCC at 2665.

Long2r arbitrary negative direction (evens) (2596-1) distal promoters

  1. Long2r0: GGGCGTG at 1076.
  2. Long2r6ci: CACGCCC at 1675.

Long2r alternate negative direction (odds) (2596-1) distal promoters

  1. Long2r7: GGGCGTG at 1789, GGGCGTG at 452.
  2. Long2r1ci: CACGCCC at 2665.

Long2r arbitrary positive direction (odds) (4050-1) distal promoters

  1. Long2r7: GGGCGTG at 1789, GGGCGTG at 452.
  2. Long2r1ci: CACGCCC at 2665.

Long2r alternate positive direction (evens) (4050-1) distal promoters

  1. Long2r0: GGGCGTG at 1076.
  2. Long2r4: GGGCGTG at 3732.
  3. Long2r6ci: CACGCCC at 1675.

p53 (Long2) analysis and results

Main article: Complex locus A1BG and ZNF497 § p53 (Long2)s

p53 response element found in the promoter of TUG1: GGGCGTG.[4]

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 1 10 0.1 0.05
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 2 2 1 1 ± 1 (--0,+-2)
Randoms Distal arbitrary negative 2 10 0.2 0.25
Randoms Distal alternate negative 3 10 0.3 0.25
Reals Distal positive 4 2 2 2 ± 1 (-+1,++3)
Randoms Distal arbitrary positive 3 10 0.3 0.3
Randoms Distal alternate positive 3 10 0.3 0.3

Comparison:

The occurrences of real p53 (Long2)s are greater than the randoms. This suggests that the real p53 (Long2)s are likely active or activable.

Acknowledgements

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

See also

References

  1. ↑ Sinéad Kearns, Rudi Lurz, Elena V. Orlova, Andrei L. Okorokov (27 July 2016). "Two p53 tetramers bind one consensus DNA response element". Nucleic Acid Research. 44 (13): 6185–6199. doi:10.1093/nar/gkw215. Retrieved 6 October 2020.
  2. ↑ 2.0 2.1 Xiaojun Zhang, Ana Carolina Dantas Machado, Yuan Ding, Yongheng Chen, Yan Lu, Yankun Duan, Kenneth W. Tham, Lin Chen, Remo Rohs, Peter Z. Qin (1 February 2014). "Conformations of p53 response elements in solution deduced using site-directed spin labeling and Monte Carlo sampling". Nucleic Acids Research. 42 (4): 2789–2797. doi:10.1093/nar/gkt1219. PMID 24293651. Retrieved 28 August 2020.
  3. ↑ Bi-He Cai, Chung-Faye Chao, Hsiang-Chi Huang, Hsueh-Yi Lee, Reiji Kannagi, and Jang-Yi Chen (27 July 2019). "Roles of p53 Family Structure and Function in Non-Canonical Response Element Binding and Activation". International Journal of Molecular Sciences. 20 (15): 3681–3700. doi:10.3390/ijms20153681. Retrieved 5 October 2020.
  4. ↑ 4.0 4.1 4.2 Jianyin Long; Daniel L. Galvan; Koki Mise; Yashpal S. Kanwar; Li Li; Naravat Poungavrin; Paul A. Overbeek; Benny H. Chang; Farhad R. Danesh (28 May 2020). "Role for carbohydrate response element-binding protein (ChREBP) in high glucose-mediated repression of long noncoding RNA Tug1" (PDF). Journal of Biological Chemistry. 5 (28). doi:10.1074/jbc.RA120.013228. Retrieved 6 October 2020.

External links

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