DAF-16 binding element gene transcriptions

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

"DAF-16 binding element (DBE), GTAAACA or TGTTTAC, and DAF-16-associated element (DAE), TGATAAG or CTTATCA, enriched in DAF-16 regulated genes [2, 4, 13, 14]. The DBE was recognized by DAF-16, and the DAE by transcription factor PQM-1 [13]."[1] Note: GTAAACA is the inverse complement (ic) of TGTTTAC and TGATAAG is the ic of CTTATCA.

Human genes

Main article: Forkhead box gene transcriptions

Gene ID: 1604 is CD55 CD55 molecule (Cromer blood group) aka DAF on 1q32.2: "This gene encodes a glycoprotein involved in the regulation of the complement cascade. Binding of the encoded protein to complement proteins accelerates their decay, thereby disrupting the cascade and preventing damage to host cells. Antigens present on this protein constitute the Cromer blood group system (CROM). Alternative splicing results in multiple transcript variants. The predominant transcript variant encodes a membrane-bound protein, but alternatively spliced transcripts may produce soluble proteins."[2]

This protein recognizes C4b and C3b fragments that condense with cell-surface hydroxyl or amino groups when nascent C4b and C3b are locally generated during C4 and C3 activation.[3] Interaction of DAF with cell-associated C4b and C3b polypeptides interferes with their ability to catalyze the conversion of C2 and factor B to enzymatically active C2a and Bb and thereby prevents the formation of C4b2a and C3bBb, the amplification convertases of the complement cascade.[3]

Gene ID: 2308 is FOXO1 forkhead box O1 on 13q14.11: "This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in myogenic growth and differentiation. Translocation of this gene with PAX3 has been associated with alveolar rhabdomyosarcoma."[4]

Consensus sequences

Main article: Consensus sequence gene transcriptions

5'-GTAAACA-3'.[1]

"Most paralogous FOX proteins bind to the canonical DNA response element 5′-RYAAAYA-3′ (R = A or G, Y = C or T)11–13."[5]

"Forkhead box protein O1 (FOXO1), a master transcriptional factor for gluconeogenesis in the liver, directly regulates TXNIP expression through the binding of the promoter region of TXNIP which contains a conserved consensus sequence, ′GTAAACAA′, of the FOXO binding site [100,101]."[6]

Hypotheses

Main article: Hypotheses
  1. A1BG has no DBEs in either promoter.
  2. A1BG is not transcribed by a DBE.
  3. DBE does not participate in the transcription of A1BG.

DBE samplings

Main article: Model samplings

Copying an apparent consensus sequence of (A/G)(C/T)AAA(C/T)A and putting it in "⌘F" finds none located between ZSCAN22 and A1BG and none between ZNF497 and A1BG as can be found by the computer programs.

Copying the consensus element GTAAACA into ⌘F found no elements in either promoter of A1BG.

For the Basic programs testing consensus sequence (A/G)(C/T)AAA(C/T)A (starting with SuccessablesDBE.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: GTAAATA at 4536.
  2. Negative strand, positive direction: ACAAACA at 4256.
  3. Positive strand, negative direction: ATAAATA at 4074, ATAAACA at 3337, ACAAATA at 3333, ATAAACA at 2876, ACAAACA at 2512, ACAAACA at 2487, GCAAACA at 2483, GCAAACA at 1539, ACAAACA at 1391.
  4. Positive strand, positive direction: ACAAATA at 2346.
  5. inverse complement, negative strand, negative direction: 0.
  6. inverse complement, negative strand, positive direction: TGTTTGC at 3340.
  7. inverse complement, positive strand, negative direction: 0.
  8. inverse complement, positive strand, positive direction: TATTTAC at 3429.

DBE (4560-2846) UTRs

  1. Negative strand, negative direction: GTAAATA at 4536, TATTTAT at 4074, TATTTGT at 3337, TGTTTAT at 3333, TATTTGT at 2876.

DBE positive direction (4265-4050) proximal promoters

  1. Negative strand, positive direction: ACAAACA at 4256.

DBE negative direction (2596-1) distal promoters

  1. Negative strand, negative direction: TGTTTGT at 2512, TGTTTGT at 2487, TGTTTGT at 1391.
  2. Positive strand, negative direction: GCAAACA at 2483, GCAAACA at 1539.

DBE positive direction (4050-1) distal promoters

  1. Negative strand, positive direction: TGTTTGC at 3340.
  2. Positive strand, positive direction: TATTTAC at 3429, ACAAATA at 2346.

DBE random dataset samplings

  1. DBEr0: 8, ACAAACA at 3652, ACAAATA at 1789, ACAAATA at 1706, ATAAATA at 1496, ACAAATA at 505, ATAAACA at 501, GTAAACA at 402, GCAAATA at 143.
  2. DBEr1: 0.
  3. DBEr2: 1, ATAAACA at 4532.
  4. DBEr3: 1, GTAAACA at 1815.
  5. DBEr4: 1, GCAAACA at 693.
  6. DBEr5: 1, ATAAATA at 3046.
  7. DBEr6: 1, GTAAATA at 2371.
  8. DBEr7: 4, ACAAACA at 3786, ATAAATA at 3631, GCAAACA at 2896, GCAAATA at 661.
  9. DBEr8: 4, GTAAATA at 4553, ATAAATA at 4523, GTAAACA at 2895, ACAAACA at 2655.
  10. DBEr9: 6, GCAAACA at 4118, ATAAACA at 3938, ACAAACA at 3458, GTAAACA at 2384, ACAAATA at 2094, ACAAACA at 1094.
  11. DBEr0ci: 1, TATTTGT at 3312.
  12. DBEr1ci: 1, TATTTAT at 3097.
  13. DBEr2ci: 4, TATTTGC at 4074, TATTTAC at 3618, TGTTTGC at 1298, TATTTGT at 1120.
  14. DBEr3ci: 3, TGTTTGT at 2268, TGTTTAT at 769, TGTTTGT at 451.
  15. DBEr4ci: 0.
  16. DBEr5ci: 3, TATTTAC at 2631, TATTTAT at 857, TGTTTAC at 717.
  17. DBEr6ci: 6, TATTTAC at 4373, TGTTTGT at 4363, TATTTAT at 1141, TATTTAT at 917, TGTTTGT at 911, TATTTAC at 188.
  18. DBEr7ci: 2, TATTTGT at 4225, TGTTTAT at 2451.
  19. DBEr8ci: 3, TGTTTGC at 1232, TATTTAC at 829, TGTTTGC at 46.
  20. DBEr9ci: 4, TGTTTAC at 3170, TGTTTAC at 2250, TATTTAC at 624, TGTTTGT at 22.

DBEr arbitrary (evens) (4560-2846) UTRs

  1. DBEr0: ACAAACA at 3652.
  2. DBEr2: ATAAACA at 4532.
  3. DBEr8: GTAAATA at 4553, ATAAATA at 4523, GTAAACA at 2895.
  4. DBEr0ci: TATTTGT at 3312.
  5. DBEr2ci: TATTTGC at 4074, TATTTAC at 3618.
  6. DBEr6ci: TATTTAC at 4373, TGTTTGT at 4363.

DBEr alternate (odds) (4560-2846) UTRs

  1. DBEr5: ATAAATA at 3046.
  2. DBEr7: ACAAACA at 3786, ATAAATA at 3631, GCAAACA at 2896.
  3. DBEr9: GCAAACA at 4118, ATAAACA at 3938, ACAAACA at 3458.
  4. DBEr1ci: TATTTAT at 3097.
  5. DBEr7ci: TATTTGT at 4225.
  6. DBEr9ci: TGTTTAC at 3170.

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

  1. DBEr6ci: TATTTAC at 4373, TGTTTGT at 4363.

DBEr arbitrary negative direction (evens) (2811-2596) proximal promoters

  1. DBEr8: ACAAACA at 2655.

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

  1. DBEr5ci: TATTTAC at 2631.

DBEr arbitrary positive direction (odds) (4265-4050) proximal promoters

  1. DBEr9: GCAAACA at 4118.
  2. DBEr7ci: TATTTGT at 4225.

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

  1. DBEr2ci: TATTTGC at 4074.

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

  1. DBEr0: ACAAATA at 1789, ACAAATA at 1706, ATAAATA at 1496, ACAAATA at 505, ATAAACA at 501, GTAAACA at 402, GCAAATA at 143.
  2. DBEr4: GCAAACA at 693.
  3. DBEr6: GTAAATA at 2371.
  4. DBEr2ci: TGTTTGC at 1298, TATTTGT at 1120.
  5. DBEr6ci: TATTTAT at 1141, TATTTAT at 917, TGTTTGT at 911, TATTTAC at 188.
  6. DBEr8ci: TGTTTGC at 1232, TATTTAC at 829, TGTTTGC at 46.

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

  1. DBEr3: GTAAACA at 1815.
  2. DBEr7: GCAAATA at 661.
  3. DBEr9: GTAAACA at 2384, ACAAATA at 2094, ACAAACA at 1094.
  4. DBEr3ci: TGTTTGT at 2268, TGTTTAT at 769, TGTTTGT at 451.
  5. DBEr5ci: TATTTAT at 857, TGTTTAC at 717.
  6. DBEr7ci: TGTTTAT at 2451.
  7. DBEr9ci: TGTTTAC at 2250, TATTTAC at 624, TGTTTGT at 22.

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

  1. DBEr3: GTAAACA at 1815.
  2. DBEr5: ATAAATA at 3046.
  3. DBEr7: ACAAACA at 3786, ATAAATA at 3631, GCAAACA at 2896, GCAAATA at 661.
  4. DBEr9: ATAAACA at 3938, ACAAACA at 3458, GTAAACA at 2384, ACAAATA at 2094, ACAAACA at 1094.
  5. DBEr1ci: TATTTAT at 3097.
  6. DBEr3ci: TGTTTGT at 2268, TGTTTAT at 769, TGTTTGT at 451.
  7. DBEr5ci: TATTTAC at 2631, TATTTAT at 857, TGTTTAC at 717.
  8. DBEr7ci: TGTTTAT at 2451.
  9. DBEr9ci: TGTTTAC at 3170, TGTTTAC at 2250, TATTTAC at 624, TGTTTGT at 22.

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

  1. DBEr0: ACAAACA at 3652, ACAAATA at 1789, ACAAATA at 1706, ATAAATA at 1496, ACAAATA at 505, ATAAACA at 501, GTAAACA at 402, GCAAATA at 143.
  2. DBEr4: GCAAACA at 693.
  3. DBEr6: GTAAATA at 2371.
  4. DBEr8: GTAAACA at 2895, ACAAACA at 2655.
  5. DBEr0ci: TATTTGT at 3312.
  6. DBEr2ci: TATTTAC at 3618, TGTTTGC at 1298, TATTTGT at 1120.
  7. DBEr6ci: TATTTAT at 1141, TATTTAT at 917, TGTTTGT at 911, TATTTAC at 188.
  8. DBEr8ci: TGTTTGC at 1232, TATTTAC at 829, TGTTTGC at 46.

Response element analysis and results

Main article: Complex locus A1BG and ZNF497 § DAF-16 binding elements

"Most paralogous FOX proteins bind to the canonical DNA response element 5′-RYAAAYA-3′ (R = A or G, Y = C or T)11–13."[5]

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 5 2 2.5 2.5
Randoms UTR arbitrary negative 10 10 1 1
Randoms UTR alternate negative 10 10 1 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 0 10 0 0.1
Randoms Core alternate positive 2 10 0.2 0.1
Reals Proximal negative 0 2 0 0
Randoms Proximal arbitrary negative 1 10 0.1 0.1
Randoms Proximal alternate negative 1 10 0.1 0.1
Reals Proximal positive 1 2 0.5 0.5
Randoms Proximal arbitrary positive 2 10 0.2 0.15
Randoms Proximal alternate positive 1 10 0.1 0.15
Reals Distal negative 5 2 2.5 2.5 ± 0.5 (--3,+-2)
Randoms Distal arbitrary negative 18 10 1.8 1.6
Randoms Distal alternate negative 14 10 1.4 1.6
Reals Distal positive 3 2 1.5 1.5 ± 0.5 (-+1,++2)
Randoms Distal arbitrary positive 23 10 2.3 2.3
Randoms Distal alternate positive 23 10 2.3 2.3

Comparison:

The occurrences of real DBEs are outside the randoms. This suggests that the real DBEs 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 Yan-Hui Li and Gai-Gai Zhang (12 April 2016). "Towards understanding the lifespan extension by reduced insulin signaling: bioinformatics analysis of DAF-16/FOXO direct targets in Caenorhabditis elegans". Oncotarget. 7 (15): 19185–19192. doi:10.18632/oncotarget.8313. PMID 2702736. Retrieved 27 August 2020.
  2. ↑ RefSeq (July 2014). "CD55 CD55 molecule (Cromer blood group) [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 18 October 2023.
  3. ↑ 3.0 3.1 "GeneCard: Molecular function for CD55 Gene".
  4. ↑ RefSeq (July 2008). "FOXO1 forkhead box O1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 3 December 2020.
  5. ↑ 5.0 5.1 Jun Li, Ana Carolina Dantas Machado, Ming Guo, Jared M. Sagendorf, Zhan Zhou, Longying Jiang, Xiaojuan Chen, Daichao Wu, Lingzhi Qu, Zhuchu Chen, Lin Chen, Remo Rohs, and Yongheng Chen (25 July 2017). "Structure of the forkhead domain of FOXA2 bound to a complete DNA consensus site". Biochemistry. 56 (29): 3745–3753. doi:10.1021/acs.biochem.7b00211. PMID 28644006. Retrieved 28 August 2020.
  6. ↑ Eiji Yoshihara (18 August 2020). "TXNIP/TBP-2: A Master Regulator for Glucose Homeostasis". Antioxidants. 9 (8): 765–84. doi:10.3390/antiox9080765. PMID 32824669 Check |pmid= value (help). Retrieved 5 September 2020.

External links

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