Retinoic acid response element gene transcriptions

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

"Retinoic acid is considered as the earliest factor for regulating anteroposterior axis of neural tube and positioning of structures in developing brain through retinoic acid response elements (RARE) consensus sequence (5′–AGGTCA–3′) in promoter regions of retinoic acid-dependent genes."[1]

"Several studies have suggested that the target gene of the RA signal generally contains two direct-repeat half sites of the consensus sequence AGGTCA that are spaced by one to five base pairs (14,16,32,38)."[2]

"Xavier-Neto’s review demonstrated that the magic AGGTCA has high affinity but poor specificity (16). Some other [nuclear receptors] NRs also utilized the RARE with the same spacer models that are used by RXRs/RARs, for example, orphan receptors, vitamin D receptors (VDR) and peroxisome proliferator-activated receptors (PPAR) (32,39). Identifying a bona fide RARE is more difficult than a simple inspection. In order to attribute the RARE in Cx43 to a candidate sequence, some observations have been conducted in our study using molecular, biological and biophysical methods and functional approaches. In a ligand-dependent luciferase assay, RARE was located between the −1,426 to −341 base pair position. The constitutively active mutant Cx43 RARE represses the luciferase activity in the absence of the ligand and has no response to the 9cRA. Our findings indicate that RARE in the Cx43 promoter is a functional element."[2]

Human genes

Additional response elements that include the 5'-AGGTCA-3' are Q elements, ROR-response elements and Thyroid hormone response elements.

Consensus sequences

A likely general consensus sequence may be AG(A/G)TCA.[2]

RARE samplings

Copying the apparent consensus sequence for the RARE (AG(A/G)TCA) and putting it in "⌘F" finds two located between ZSCAN22 and A1BG and three between ZNF497 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence AGATCA (starting with SuccessablesRARE.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 AGATCA, 0.
  2. positive strand, negative direction, looking for AGATCA, 6, AGATCA at 3489, AGATCA at 3277, AGATCA at 2414, AGATCA at 1988, AGATCA at 878, AGATCA at 590.
  3. positive strand, positive direction, looking for AGATCA, 1, AGATCA at 2168.
  4. negative strand, positive direction, looking for AGATCA, 1, AGATCA at 2231.
  5. complement, negative strand, negative direction, looking for TCTAGT, 6, TCTAGT at 3489, TCTAGT at 3277, TCTAGT at 2414, TCTAGT at 1988, TCTAGT at 878, TCTAGT at 590.
  6. complement, positive strand, negative direction, looking for TCTAGT, 0.
  7. complement, positive strand, positive direction, looking for TCTAGT, 1, TCTAGT at 2231.
  8. complement, negative strand, positive direction, looking for TCTAGT, 1, TCTAGT at 2168.
  9. inverse complement, negative strand, negative direction, looking for TGATCT, 1, TGATCT at 3463.
  10. inverse complement, positive strand, negative direction, looking for TGATCT, 1, TGATCT at 1482.
  11. inverse complement, positive strand, positive direction, looking for TGATCT, 0.
  12. inverse complement, negative strand, positive direction, looking for TGATCT, 0.
  13. inverse negative strand, negative direction, looking for ACTAGA, 1, ACTAGA at 1482.
  14. inverse positive strand, negative direction, looking for ACTAGA, 1, ACTAGA at 3463.
  15. inverse positive strand, positive direction, looking for ACTAGA, 0.
  16. inverse negative strand, positive direction, looking for ACTAGA, 0.

RARE (4560-2846) UTRs

  1. Negative strand, negative direction: TGATCT at 3463.
  2. Positive strand, negative direction: AGATCA at 3489, AGATCA at 3277.

RARE negative direction (2596-1) distal promoters

  1. Positive strand, negative direction: AGATCA at 2414, AGATCA at 1988, AGATCA at 878, AGATCA at 590.
  2. Positive strand, negative direction: TGATCT at 1482.

RARE positive direction (4050-1) distal promoters

  1. Negative strand, positive direction: AGATCA at 2231.
  2. Positive strand, positive direction: AGATCA at 2168.

RARE random dataset samplings

  1. RAREr0: 2, AGATCA at 1853, AGGTCA at 699.
  2. RAREr1: 3, AGATCA at 2996, AGATCA at 1780, AGGTCA at 1750.
  3. RAREr2: 2, AGGTCA at 4381, AGGTCA at 3163.
  4. RAREr3: 1, AGGTCA at 2303.
  5. RAREr4: 0.
  6. RAREr5: 2, AGGTCA at 4296, AGATCA at 1747.
  7. RAREr6: 1, AGATCA at 4311.
  8. RAREr7: 0.
  9. RAREr8: 2, AGATCA at 1501, AGATCA at 865.
  10. RAREr9: 0.
  11. RAREr0ci: 0.
  12. RAREr1ci: 2, TGATCT at 4399, TGATCT at 2627.
  13. RAREr2ci: 2, TGATCT at 3762, TGATCT at 1193.
  14. RAREr3ci: 4, TGACCT at 4439, TGATCT at 4373, TGACCT at 2443, TGATCT at 1126.
  15. RAREr4ci: 0.
  16. RAREr5ci: 1, TGACCT at 2538.
  17. RAREr6ci: 2, TGATCT at 3048, TGATCT at 880.
  18. RAREr7ci: 2, TGACCT at 3801, TGATCT at 1003.
  19. RAREr8ci: 2, TGATCT at 2193, TGACCT at 540.
  20. RAREr9ci: 0.

RAREr arbitrary (evens) (4560-2846) UTRs

  1. RAREr2: AGGTCA at 4381, AGGTCA at 3163.
  2. RAREr6: AGATCA at 4311.
  3. RAREr2ci: TGATCT at 3762.

RAREr alternate (odds) (4560-2846) UTRs

  1. RAREr1: AGATCA at 2996.
  2. RAREr5: AGGTCA at 4296.
  3. RAREr1ci: TGATCT at 4399.
  4. RAREr3ci: TGACCT at 4439, TGATCT at 4373.
  5. RAREr7ci: TGACCT at 3801.

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

  1. RAREr5: AGGTCA at 4296.
  2. RAREr1ci: TGATCT at 4399.
  3. RAREr3ci: TGACCT at 4439, TGATCT at 4373.

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

  1. RAREr2: AGGTCA at 4381.
  2. RAREr6: AGATCA at 4311.

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

  1. RAREr1ci: TGATCT at 2627.

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

  1. RAREr0: AGATCA at 1853, AGGTCA at 699.
  2. RAREr8: AGATCA at 1501, AGATCA at 865.
  3. RAREr8ci: TGATCT at 2193, TGACCT at 540.

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

  1. RAREr1: AGATCA at 1780, AGGTCA at 1750.
  2. RAREr3: AGGTCA at 2303.
  3. RAREr5: AGATCA at 1747.
  4. RAREr3ci: TGACCT at 2443, TGATCT at 1126.
  5. RAREr5ci: TGACCT at 2538.
  6. RAREr7ci: TGATCT at 1003.

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

  1. RAREr1: AGATCA at 2996, AGATCA at 1780, AGGTCA at 1750.
  2. RAREr3: AGGTCA at 2303.
  3. RAREr5: AGATCA at 1747.
  4. RAREr1ci: TGATCT at 2627.
  5. RAREr3ci: TGACCT at 2443, TGATCT at 1126.
  6. RAREr5ci: TGACCT at 2538.
  7. RAREr7ci: TGACCT at 3801, TGATCT at 1003.

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

  1. RAREr0: AGATCA at 1853, AGGTCA at 699.
  2. RAREr2: AGGTCA at 3163.
  3. RAREr8: AGATCA at 1501, AGATCA at 865.
  4. RAREr2ci: TGATCT at 3762, TGATCT at 1193.
  5. RAREr8ci: TGATCT at 2193, TGACCT at 540.

RARE analysis and results

Main article: Complex locus A1BG and ZNF497 § RAREs

A likely general consensus sequence may be AG(A/G)TCA.[2]

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 3 2 1.5 1.5 ± 0.5 (--1,+-2)
Randoms UTR arbitrary negative 4 10 0.4 0.5
Randoms UTR alternate negative 6 10 0.6 0.5
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 4 10 0.4 0.3
Randoms Core alternate positive 2 10 0.2 0.3
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 5 2 2.5 2.5 ± 2.5 (--0,+-5)
Randoms Distal arbitrary negative 6 10 0.6 0.7
Randoms Distal alternate negative 8 10 0.8 0.7
Reals Distal positive 2 2 1 1 (-+1,++1)
Randoms Distal arbitrary positive 11 10 1.1 1.0
Randoms Distal alternate positive 9 10 0.9 1.0

Comparison:

The occurrences of real RARE UTRs and negative direction distals are greater than the randoms, positive direction distals are random. This suggests that the real RAREs are likely active or activable.

Acknowledgements

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

See also

References

  1. ↑ Ashutosh Kumar, Himanshu N. Singh, Vikas Pareek, Khursheed Raza, Subrahamanyam Dantham, Pavan Kumar, Sankat Mochan and Muneeb A. Faiq (9 August 2016). "A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome". Frontiers in Human Neuroscience. 10: 403. doi:10.3389/fnhum.2016.00403. PMID 27555815. Retrieved 7 September 2020.
  2. ↑ 2.0 2.1 2.2 2.3 Ruoyi Gu, Jun Xu, Yixiang Lin, Jing Zhang, Huijun Wang, Wei Sheng, Duan Ma, Xiaojing Ma & Guoying Huang (July 2016). "Liganded retinoic acid X receptor α represses connexin 43 through a potential retinoic acid response element in the promoter region". Pediatric Research. 80 (1): 159–168. doi:10.1038/pr.2016.47. PMID 26991262. Retrieved 7 September 2020.

External links

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