HY box gene transcriptions

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Editor-In-Chief: Henry A. Hoff

"Deletion, mutagenesis, and tandem repeat analyses identified the core responsive element as the region between −89 and −60 bp (termed the hypertrophy box [HY box]), which showed specific binding to RUNX‐2."[1]

The "HY box is the core element responsive to RUNX‐2 in human COL10A1 promoter."[1]

Boxes

Main articles: Box gene transcriptions and Boxes

A repeating sequence of nucleotides that forms a transcription or a regulatory signal is a box.

Consensus sequences

Main article: Consensus sequences

"Deletion analysis by a series of 5′-deletion constructs identified the responsive region to RUNX-2 as being between −81 bp and −76 bp, containing a putative RUNX-2 binding sequence (TGAGGG), which is similar to that identified in the promoter region of human interleukin-3 (TGTGGG) (33)."[1] This suggests a consensus sequence of 3'-TG(A/T)GGG-5' on the template strand in the direction of transcription.

RUNX2

The gene RUNX2 "is a member of the RUNX family of transcription factors and encodes a nuclear protein with an Runt DNA-binding domain. This protein is essential for osteoblastic differentiation and skeletal morphogenesis and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. The protein can bind DNA both as a monomer or, with more affinity, as a subunit of a heterodimeric complex."[2]

COL10A1

The gene COL10A1 "encodes the alpha chain of type X collagen, a short chain collagen expressed by hypertrophic chondrocytes during endochondral ossification. Unlike type VIII collagen, the other short chain collagen, type X collagen is a homotrimer."[3]

Human COL10A1, GeneID: 1300, has an HY box as the core responsive element.[1]

Hypotheses

Main article: Hypotheses
  1. A1BG is not transcribed by an HY box.

HY box samplings

For the Basic programs (starting with SuccessablesHY.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 is SuccessablesHY--.bas, looking for TG(A/T)GGG, 1, TGTGGG at 749.
  2. negative strand in the positive direction is SuccessablesHY-+.bas, looking for TG(A/T)GGG, 5, TGTGGG at 4395, TGAGGG at 3906, TGAGGG at 3879, TGAGGG at 3479, TGAGGG at 258.
  3. positive strand in the negative direction is SuccessablesHY+-.bas, looking for TG(A/T)GGG, 5, TGAGGG at 4558, TGTGGG at 3712, TGAGGG at 3652, TGAGGG at 2699, TGAGGG at 88.
  4. positive strand in the positive direction is SuccessablesHY++.bas, looking for TG(A/T)GGG, 2, TGTGGG at 3533, TGTGGG at 2965.
  5. inverse complement, negative strand, negative direction is SuccessablesHYci--.bas, looking for CCC(A/T)CA, 4, CCCTCA at 4498, CCCTCA at 3889, CCCACA at 3184, CCCTCA at 2702.
  6. inverse complement, negative strand, positive direction is SuccessablesHYci-+.bas, looking for CCC(A/T)CA, 3, CCCTCA at 3503, CCCTCA at 3207, CCCTCA at 88.
  7. inverse complement, positive strand, negative direction is SuccessablesHYci+-.bas, looking for CCC(A/T)CA, 0,
  8. inverse complement, positive strand, positive direction is SuccessablesHYci++.bas, looking for CCC(A/T)CA, 5, CCCTCA at 3185, CCCACA at 1803, CCCTCA at 1783, CCCTCA at 662, CCCTCA at 494.

HY box UTRs

  1. Negative strand, negative direction: CCCTCA at 4498, CCCTCA at 3889, CCCACA at 3184.
  2. Positive strand, negative direction: TGAGGG at 4558, TGTGGG at 3712, TGAGGG at 3652.

HY box core promoters

  1. Negative strand, positive direction: TGTGGG at 4395.

HY box proximal promoters

  1. Negative strand, negative direction: CCCTCA at 2702.
  2. Positive strand, negative direction: TGAGGG at 2699.

HY box distal promoters

  1. Negative strand, negative direction: TGTGGG at 749.
  2. Positive strand, negative direction: TGAGGG at 88.
  1. Negative strand, positive direction: TGAGGG at 3906, TGAGGG at 3879, CCCTCA at 3503, TGAGGG at 3479, CCCTCA at 3207, TGAGGG at 258, CCCTCA at 88.
  2. Positive strand, positive direction: TGTGGG at 3533, CCCTCA at 3185, TGTGGG at 2965, CCCACA at 1803, CCCTCA at 1783, CCCTCA at 662, CCCTCA at 494.

HY boxes random dataset samplings

  1. HYboxr0: 0.
  2. HYboxr1: 2, TGTGGG at 873, TGTGGG at 699.
  3. HYboxr2: 4, TGAGGG at 2839, TGAGGG at 2396, TGTGGG at 2001, TGAGGG at 170.
  4. HYboxr3: 4, TGTGGG at 3855, TGAGGG at 2864, TGAGGG at 2319, TGTGGG at 513.
  5. HYboxr4: 2, TGTGGG at 2762, TGTGGG at 1825.
  6. HYboxr5: 4, TGAGGG at 3839, TGAGGG at 2381, TGTGGG at 1723, TGAGGG at 517.
  7. HYboxr6: 0.
  8. HYboxr7: 5, TGAGGG at 4318, TGTGGG at 4228, TGAGGG at 1728, TGAGGG at 1189, TGAGGG at 631.
  9. HYboxr8: 2, TGAGGG at 4205, TGAGGG at 2864.
  10. HYboxr9: 2, TGTGGG at 4391, TGAGGG at 227.
  11. HYboxr0ci: 3, CCCACA at 3394, CCCTCA at 2874, CCCTCA at 588.
  12. HYboxr1ci: 3, CCCACA at 4235, CCCTCA at 2736, CCCTCA at 425.
  13. HYboxr2ci: 2, CCCTCA at 4479, CCCACA at 3836.
  14. HYboxr3ci: 3, CCCACA at 4283, CCCTCA at 1522, CCCACA at 434.
  15. HYboxr4ci: 5, CCCACA at 4198, CCCTCA at 1909, CCCTCA at 1526, CCCACA at 907, CCCACA at 236.
  16. HYboxr5ci: 0.
  17. HYboxr6ci: 10, CCCTCA at 3984, CCCACA at 3628, CCCTCA at 2970, CCCACA at 2312, CCCACA at 1776, CCCTCA at 1737, CCCACA at 1670, CCCACA at 1297, CCCACA at 1166, CCCTCA at 887.
  18. HYboxr7ci: 7, CCCACA at 3641, CCCTCA at 2910, CCCACA at 2680, CCCTCA at 1748, CCCACA at 1204, CCCTCA at 979, CCCACA at 814.
  19. HYboxr8ci: 2, CCCTCA at 3757, CCCACA at 1903.
  20. HYboxr9ci: 5, CCCACA at 3449, CCCACA at 1674, CCCACA at 1520, CCCTCA at 192, CCCTCA at 102.

HYboxr arbitrary UTRs

  1. HYboxr8: TGAGGG at 4205, TGAGGG at 2864.
  2. HYboxr0ci: CCCACA at 3394, CCCTCA at 2874.
  3. HYboxr2ci: CCCTCA at 4479, CCCACA at 3836.
  4. HYboxr4ci: CCCACA at 4198.
  5. HYboxr6ci: CCCTCA at 3984, CCCACA at 3628, CCCTCA at 2970.
  6. HYboxr8ci: CCCTCA at 3757.

HYboxr alternate UTRs

  1. HYboxr3: TGTGGG at 3855, TGAGGG at 2864.
  2. HYboxr5: TGAGGG at 3839.
  3. HYboxr7: TGAGGG at 4318, TGTGGG at 4228.
  4. HYboxr9: TGTGGG at 4391.
  5. HYboxr1ci: CCCACA at 4235.
  6. HYboxr3ci: CCCACA at 4283.
  7. HYboxr7ci: CCCACA at 3641, CCCTCA at 2910.
  8. HYboxr9ci: CCCACA at 3449.

HYboxr arbitrary negative direction core promoters

  1. HYboxr2: TGAGGG at 2839.

HYboxr arbitrary positive direction core promoters

  1. HYboxr7: TGAGGG at 4318.
  2. HYboxr9: TGTGGG at 4391.

HYboxr arbitrary negative direction proximal promoters

  1. HYboxr4: TGTGGG at 2762.

HYboxr alternate negative direction proximal promoters

  1. HYboxr1ci: CCCTCA at 2736.
  2. HYboxr7ci: CCCACA at 2680.

HYboxr arbitrary positive direction proximal promoters

  1. HYboxr7: TGTGGG at 4228.
  2. HYboxr1ci: CCCACA at 4235.

HYboxr alternate positive direction proximal promoters

  1. HYboxr8: TGAGGG at 4205.
  2. HYboxr4ci: CCCACA at 4198.

HYboxr arbitrary negative direction distal promoters

  1. HYboxr2: TGAGGG at 2396, TGTGGG at 2001, TGAGGG at 170.
  2. HYboxr4: TGTGGG at 1825.
  3. HYboxr0ci: CCCTCA at 588.
  4. HYboxr4ci: CCCTCA at 1909, CCCTCA at 1526, CCCACA at 907, CCCACA at 236.
  5. HYboxr6ci: CCCACA at 2312, CCCACA at 1776, CCCTCA at 1737, CCCACA at 1670, CCCACA at 1297, CCCACA at 1166, CCCTCA at 887.
  6. HYboxr8ci: CCCACA at 1903.

HYboxr alternate negative direction distal promoters

  1. HYboxr3: TGAGGG at 2319, TGTGGG at 513.
  2. HYboxr5: TGAGGG at 2381, TGTGGG at 1723, TGAGGG at 517.
  3. HYboxr7: TGAGGG at 1728, TGAGGG at 1189, TGAGGG at 631.
  4. HYboxr9: TGAGGG at 227.
  5. HYboxr1ci: CCCTCA at 425.
  6. HYboxr3ci: CCCTCA at 1522, CCCACA at 434.
  7. HYboxr7ci: CCCTCA at 1748, CCCACA at 1204, CCCTCA at 979, CCCACA at 814.
  8. HYboxr9ci: CCCACA at 1674, CCCACA at 1520, CCCTCA at 192, CCCTCA at 102.

HYboxr arbitrary positive direction distal promoters

  1. HYboxr1: TGTGGG at 873, TGTGGG at 699.
  2. HYboxr3: TGTGGG at 3855, TGAGGG at 2864, TGAGGG at 2319, TGTGGG at 513.
  3. HYboxr5: TGAGGG at 3839, TGAGGG at 2381, TGTGGG at 1723, TGAGGG at 517.
  4. HYboxr7: TGAGGG at 1728, TGAGGG at 1189, TGAGGG at 631.
  5. HYboxr9: TGAGGG at 227.
  6. HYboxr1ci: CCCTCA at 2736, CCCTCA at 425.
  7. HYboxr3ci: CCCTCA at 1522, CCCACA at 434.
  8. HYboxr7ci: CCCACA at 3641, CCCTCA at 2910, CCCACA at 2680, CCCTCA at 1748, CCCACA at 1204, CCCTCA at 979, CCCACA at 814.
  9. HYboxr9ci: CCCACA at 3449, CCCACA at 1674, CCCACA at 1520, CCCTCA at 192, CCCTCA at 102.

HYboxr alternate positive direction distal promoters

  1. HYboxr2: TGAGGG at 2839, TGAGGG at 2396, TGTGGG at 2001, TGAGGG at 170.
  2. HYboxr4: TGTGGG at 2762, TGTGGG at 1825.
  3. HYboxr8: TGAGGG at 2864.
  4. HYboxr0ci: CCCACA at 3394, CCCTCA at 2874, CCCTCA at 588.
  5. HYboxr2ci: CCCACA at 3836.
  6. HYboxr4ci: CCCTCA at 1909, CCCTCA at 1526, CCCACA at 907, CCCACA at 236.
  7. HYboxr6ci: CCCTCA at 3984, CCCACA at 3628, CCCTCA at 2970, CCCACA at 2312, CCCACA at 1776, CCCTCA at 1737, CCCACA at 1670, CCCACA at 1297, CCCACA at 1166, CCCTCA at 887.

HY boxes analysis and results

Main article: Complex locus A1BG and ZNF497 § HY boxes

"Deletion analysis by a series of 5′-deletion constructs identified the responsive region to RUNX-2 as being between −81 bp and −76 bp, containing a putative RUNX-2 binding sequence (TGAGGG), which is similar to that identified in the promoter region of human interleukin-3 (TGTGGG) (33)."[1] This suggests a consensus sequence of TG(A/T)GGG.

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 6 2 3 3 ± 0 (--3,+-3)
Randoms UTR arbitrary negative 11 10 1.1 1.1
Randoms UTR alternate negative 11 10 1.1 1.1
Reals Core negative 0 2 0 0
Randoms Core arbitrary negative 1 10 0.1 0.05
Randoms Core alternate negative 0 10 0 0.05
Reals Core positive 1 2 0.5 0.5 ± 0.5 (-+1,++0)
Randoms Core arbitrary positive 2 10 0.2 0.1
Randoms Core alternate positive 0 10 0 0.1
Reals Proximal negative 2 2 1 1 ± 0 (--1,+-1)
Randoms Proximal arbitrary negative 1 10 0.1 0.15
Randoms Proximal alternate negative 2 10 0.2 0.15
Reals Proximal positive 0 2 0 0
Randoms Proximal arbitrary positive 2 10 0.2 0.2
Randoms Proximal alternate positive 2 10 0.2 0.2
Reals Distal negative 2 2 1 1 ± 0 (--1,+-1)
Randoms Distal arbitrary negative 17 10 1.7 1.85
Randoms Distal alternate negative 20 10 2.0 1.85
Reals Distal positive 14 2 7 7 ± 0 (-+7,++7)
Randoms Distal arbitrary positive 30 10 3.0 2.75
Randoms Distal alternate positive 25 10 2.5 2.75

Comparison:

The occurrences of real HY box UTRs, cores, proximals and positive distals are greater than the randoms, negative distals are less than randoms. This suggests that the real HY boxes 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 Akiro Higashikawa, Taku Saito, Toshiyuki Ikeda, Satoru Kamekura, Naohiro Kawamura, Akinori Kan, Yasushi Oshima, Shinsuke Ohba, Naoshi Ogata, Katsushi Takeshita, Kozo Nakamura, Ung-Il Chung, Hiroshi Kawaguchi (2009). "Identification of the core element responsive to runt-related transcription factor 2 in the promoter of human type x collagen gene". Arthritis & Rheumatism. 60 (1): 166–78. doi:10.1002/art.24243. PMID 19116917. Retrieved 2013-06-18. Unknown parameter |month= ignored (help)
  2. ↑ "RUNX2 runt-related transcription factor 2 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. 2013. Retrieved 2013-06-18. Unknown parameter |month= ignored (help)
  3. ↑ HGNC (June 9, 2013). "COL10A1 collagen, type X, alpha 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2013-06-18.

External links

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