GAAC element gene transcriptions

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Editor-In-Chief: Henry A. Hoff

This micrograph stained with chlorazol black, reveals an Entamoeba histolytica cyst. Credit: CDC/ Dr. George Healy.

The GAAC element is usually a core promoter element containing guanine (G), adenine (A), and cytosine (C), "able to direct a new transcription start site 2-7 bases downstream of itself, independent of TATA and Inr regions."[1]

Genetics

File:Bob, the guinea pig.jpg
This is an image of Bob, the guinea pig. Credit: selbst.

Genetics involves the expression, transmission, and variation of inherited characteristics.

Def. a "branch of biology that deals with the transmission and variation of inherited characteristics, in particular chromosomes and DNA"[2] is called genetics.

Promoters

File:Preinitiation complex.png
The diagram shows the RNA polymerase II holoenzyme attached to the DNA template strand. Credit: ArneLH.

Although human DNA like most other life forms on Earth has two strands forming a double helix, only one of the strands, the template strand, is usually used to transcribe a gene product such as messenger ribonucleic acid (mRNA).

On the template strand is a nucleotide sequence (the gene promoter) that is usually interacted with by the transcription mechanism before any product of the gene is transcribed.

Consensus sequences

The consensus sequence in the direction of transcription on the template strand is 3'-GAACT-5'.[1] T is thymine.

Dispersed promoters

A dispersed promoter contains "several start sites over 50–100 nucleotides and [is] typically found in CpG islands in vertebrates".[3] "CpGs are ... relatively enriched around the TSS. In fact, the enrichment pattern peaks sharply close to the core promoter 15 bp upstream of the TSS".[4] Normally a C (cytosine) base followed immediately by a G (guanine) base (a CpG) is rare in vertebrate DNA because the cytosines in such an arrangement tend to be methylated.

"[I]n vertebrates dispersed promoters are more common than focused promoters."[3]

General transcription factors II D

This element also controls the rate of transcription initiation and interacts in a sequence-specific manner with the transcription factor II D (TFIID) complex.[1]

Entamoeba histolytica

The GAAC element is present "in 31/37 protein-encoding E. histolytica genes ... It has a variable location between the TATA box and the Inr sequences".[1]

Human genes

"The genes encoding the two type I collagen chains are selectively activated in ... fibroblasts and osteoblasts [within the promoter by] a sequence located between -3.2 and -2.3 kb".[5] "[T]wo short elements ... tendon-specific element (TSE) 1 and TSE2 [within this sequence are] necessary to direct reporter gene expression".[5] The binding sequence of TSE2 "corresponded to an E-box."[5] TSE1 and TSE2 need to cooperate with each other and "other cis-acting elements of the proximal promoter to activate gene expression in tendon fibroblasts."[5] "[A] short sequence [in TSE1 contains] a GAACT motif that [binds] a tendon-specific nuclear protein."[5]

Hypotheses

  1. A1BG has no GAAC elements in either promoter.
  2. A1BG is not transcribed by a GAAC element.
  3. A GAAC element does not participate in the transcription of A1BG.

GAAC element samplings

The GAAC element is usually a core promoter element containing guanine (G), adenine (A), and cytosine (C), "able to direct a new transcription start site 2-7 bases downstream of itself, independent of TATA and Inr regions."[1]

For the Basic programs (starting with SuccessablesGAAC.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 (from ZSCAN22 to A1BG) is SuccessablesGAAC--.bas, looking for GAACT, 13, GAACT at 4294, GAACT at 4012, GAACT at 3571, GAACT at 3401, GAACT at 3242, GAACT at 3103, GAACT at 2714, GAACT at 2580, GAACT at 2379, GAACT at 2127, GAACT at 1300, GAACT at 1009, GAACT at 843.
  2. positive strand, negative direction is SuccessablesGAAC+-.bas, looking for GAACT, 2, GAACT at 3460, GAACT at 1685.
  3. negative strand, positive direction (from ZNF497 to A1BG) is SuccessablesGAAC-+.bas, looking for GAACT, 2, GAACT at 4048, GAACT at 1951.
  4. positive strand, positive direction is SuccessablesGAAC++.bas, looking for GAACT, 2, GAACT at 4131, GAACT at 4016.
  5. inverse complement, negative strand, negative direction is SuccessablesGAACci--.bas, looking for AGTTC, 3, AGTTC at 4178, AGTTC at 4027, AGTTC at 3844.
  6. inverse complement, positive strand, negative direction is SuccessablesGAACci+-.bas, looking for AGTTC, 6, AGTTC at 4417, AGTTC at 4175, AGTTC at 4024, AGTTC at 1177, AGTTC at 719, AGTTC at 253.
  7. inverse complement, negative strand, positive direction is SuccessablesGAACci-+.bas, looking for AGTTC, 3, AGTTC at 4200, AGTTC at 2954, AGTTC at 1987.
  8. inverse complement, positive strand, positive direction is SuccessablesGAACci++.bas, looking for AGTTC, 2, AGTTC at 2615, AGTTC at 2508.

GAAC (4560-2846) UTRs

  1. Negative strand, negative direction: GAACT at 4294, GAACT at 4012, GAACT at 3571, GAACT at 3401, GAACT at 3242, GAACT at 3103.
  2. Negative strand, negative direction: AGTTC at 4178, AGTTC at 4027, AGTTC at 3844.
  3. Positive strand, negative direction: GAACT at 3460.
  4. Positive strand, negative direction: AGTTC at 4417, AGTTC at 4175, AGTTC at 4024.

GAAC positive direction (4445-4265) core promoters

  1. Positive strand, positive direction: AGTTC at 2615, AGTTC at 2508.

GAAC negative direction (2811-2596) proximal promoters

  1. Negative strand, negative direction: GAACT at 2714.

GAAC positive direction (4265-4050) proximal promoters

  1. Negative strand, positive direction: AGTTC at 4200.
  2. Positive strand, positive direction: GAACT at 4131.

GAAC negative direction (2596-1) distal promoters

  1. Negative strand, negative direction: GAACT at 2580, GAACT at 2379, GAACT at 2127, GAACT at 1300, GAACT at 1009, GAACT at 843.
  2. Positive strand, negative direction: GAACT at 1685.
  3. Positive strand, negative direction: AGTTC at 1177, AGTTC at 719, AGTTC at 253.

GAAC positive direction (4050-1) distal promoters

  1. Negative strand, positive direction: GAACT at 4048, GAACT at 1951.
  2. Negative strand, positive direction: AGTTC at 2954, AGTTC at 1987.
  3. Positive strand, positive direction: GAACT at 4016.
  4. Positive strand, positive direction: AGTTC at 2615, AGTTC at 2508.

GAAC element random dataset samplings

  1. GAACr0: 6, GAACT at 3494, GAACT at 3230, GAACT at 2501, GAACT at 1331, GAACT at 1302, GAACT at 897.
  2. GAACr1: 4, GAACT at 1035, GAACT at 940, GAACT at 471, GAACT at 95.
  3. GAACr2: 3, GAACT at 4058, GAACT at 3023, GAACT at 2237.
  4. GAACr3: 4, GAACT at 4531, GAACT at 1900, GAACT at 716, GAACT at 221.
  5. GAACr4: 6, GAACT at 3815, GAACT at 2998, GAACT at 1747, GAACT at 1740, GAACT at 579, GAACT at 267.
  6. GAACr5: 6, GAACT at 3798, GAACT at 1941, GAACT at 1892, GAACT at 826, GAACT at 342, GAACT at 48.
  7. GAACr6: 1, GAACT at 3096.
  8. GAACr7: 2, GAACT at 3198, GAACT at 2384.
  9. GAACr8: 3, GAACT at 2053, GAACT at 1342, GAACT at 885.
  10. GAACr9: 5, GAACT at 3840, GAACT at 3653, GAACT at 2102, GAACT at 1870, GAACT at 279.
  11. GAACr0ci: 3, AGTTC at 2457, AGTTC at 1130, AGTTC at 687.
  12. GAACr1ci: 4, AGTTC at 1971, AGTTC at 855, AGTTC at 560, AGTTC at 323.
  13. GAACr2ci: 1, AGTTC at 878.
  14. GAACr3ci: 6, AGTTC at 4541, AGTTC at 4218, AGTTC at 4158, AGTTC at 3987, AGTTC at 1538, AGTTC at 1018.
  15. GAACr4ci: 1, AGTTC at 3438.
  16. GAACr5ci: 3, AGTTC at 4076, AGTTC at 3768, AGTTC at 3088.
  17. GAACr6ci: 4, AGTTC at 4022, AGTTC at 3090, AGTTC at 2162, AGTTC at 143.
  18. GAACr7ci: 4, AGTTC at 3747, AGTTC at 2571, AGTTC at 1824, AGTTC at 1752.
  19. GAACr8ci: 6, AGTTC at 2793, AGTTC at 2550, AGTTC at 1757, AGTTC at 1371, AGTTC at 623, AGTTC at 116.
  20. GAACr9ci: 3, AGTTC at 4285, AGTTC at 3128, AGTTC at 1878.

GAACr arbitrary (evens) (4560-2846) UTRs

  1. GAACr0: GAACT at 3494, GAACT at 3230.
  2. GAACr2: GAACT at 4058, GAACT at 3023.
  3. GAACr4: GAACT at 3815, GAACT at 2998.
  4. GAACr6: GAACT at 3096.
  5. GAACr4ci: AGTTC at 3438.
  6. GAACr6ci: AGTTC at 4022, AGTTC at 3090.

GAACr alternate (odds) (4560-2846) UTRs

  1. GAACr3: GAACT at 4531.
  2. GAACr5: GAACT at 3798.
  3. GAACr7: GAACT at 3198.
  4. GAACr9: GAACT at 3840, GAACT at 3653.
  5. GAACr3ci: AGTTC at 4541, AGTTC at 4218, AGTTC at 4158, AGTTC at 3987.
  6. GAACr5ci: AGTTC at 4076, AGTTC at 3768, AGTTC at 3088.
  7. GAACr7ci: AGTTC at 3747.
  8. GAACr9ci: AGTTC at 4285, AGTTC at 3128.

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

  1. GAACr9ci: AGTTC at 4285.

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

  1. GAACr8ci: AGTTC at 2793.

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

  1. GAACr3ci: AGTTC at 4218, AGTTC at 4158.
  2. GAACr5ci: AGTTC at 4076.

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

  1. GAACr2: GAACT at 4058.

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

  1. GAACr0: GAACT at 2501, GAACT at 1331, GAACT at 1302, GAACT at 897.
  2. GAACr2: GAACT at 2237.
  3. GAACr4: GAACT at 1747, GAACT at 1740, GAACT at 579, GAACT at 267.
  4. GAACr8: GAACT at 2053, GAACT at 1342, GAACT at 885.
  5. GAACr0ci: AGTTC at 2457, AGTTC at 1130, AGTTC at 687.
  6. GAACr2ci: AGTTC at 878.
  7. GAACr6ci: AGTTC at 2162, AGTTC at 143.
  8. GAACr8ci: AGTTC at 2550, AGTTC at 1757, AGTTC at 1371, AGTTC at 623, AGTTC at 116.

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

  1. GAACr1: GAACT at 1035, GAACT at 940, GAACT at 471, GAACT at 95.
  2. GAACr3: GAACT at 1900, GAACT at 716, GAACT at 221.
  3. GAACr5: GAACT at 1941, GAACT at 1892, GAACT at 826, GAACT at 342, GAACT at 48.
  4. GAACr7: GAACT at 2384.
  5. GAACr9: GAACT at 2102, GAACT at 1870, GAACT at 279.
  6. GAACr1ci: AGTTC at 1971, AGTTC at 855, AGTTC at 560, AGTTC at 323.
  7. GAACr3ci: AGTTC at 1538, AGTTC at 1018.
  8. GAACr7ci: AGTTC at 2571, AGTTC at 1824, AGTTC at 1752.
  9. GAACr9ci: AGTTC at 1878.

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

  1. GAACr1: GAACT at 1035, GAACT at 940, GAACT at 471, GAACT at 95.
  2. GAACr3: GAACT at 1900, GAACT at 716, GAACT at 221.
  3. GAACr5: GAACT at 3798, GAACT at 1941, GAACT at 1892, GAACT at 826, GAACT at 342, GAACT at 48.
  4. GAACr7: GAACT at 3198, GAACT at 2384.
  5. GAACr9: GAACT at 3840, GAACT at 3653, GAACT at 2102, GAACT at 1870, GAACT at 279.
  6. GAACr1ci: AGTTC at 1971, AGTTC at 855, AGTTC at 560, AGTTC at 323.
  7. GAACr3ci: AGTTC at 3987, AGTTC at 1538, AGTTC at 1018.
  8. GAACr5ci: AGTTC at 3768, AGTTC at 3088.
  9. GAACr7ci: AGTTC at 3747, AGTTC at 2571, AGTTC at 1824, AGTTC at 1752.
  10. GAACr9ci: AGTTC at 3128, AGTTC at 1878.

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

  1. GAACr0: GAACT at 3494, GAACT at 3230, GAACT at 2501, GAACT at 1331, GAACT at 1302, GAACT at 897.
  2. GAACr2: GAACT at 3023, GAACT at 2237.
  3. GAACr4: GAACT at 3815, GAACT at 2998, GAACT at 1747, GAACT at 1740, GAACT at 579, GAACT at 267.
  4. GAACr6: GAACT at 3096.
  5. GAACr8: GAACT at 2053, GAACT at 1342, GAACT at 885.
  6. GAACr0ci: AGTTC at 2457, AGTTC at 1130, AGTTC at 687.
  7. GAACr2ci: AGTTC at 878.
  8. GAACr4ci: AGTTC at 3438.
  9. GAACr6ci: AGTTC at 4022, AGTTC at 3090, AGTTC at 2162, AGTTC at 143.
  10. GAACr8ci: AGTTC at 2793, AGTTC at 2550, AGTTC at 1757, AGTTC at 1371, AGTTC at 623, AGTTC at 116.

GAAC element analysis and results

The GAAC portion of the GAAC element is the inverse of the Homeobox motif.

The GAAC portion of the GAAC element is in the Androgen response elements AGAACANNNTGTTCT,[6] the Glucocorticoid response elements AGAACA, the Heat shock elements nGAAn-(5-bp)-nGAAnnTTCn (Eastmond), the Leu3 transcription factors, the Rap1 reduced consensus (A/G)(A/C)ACCC(A/G)N(A/G)C(A/C)(C/T)(A/C)[7] had one result GAACCCACACCTC in the positive direction at 1807, less than half way from ZNF497, the Vitamin D response elements

"DNA-binding by the GR-DBD has been well-characterized; it is highly sequence-specific, directly recognizing invariant guanine nucleotides of two AGAACA [TGTTCT] half sites called the glucocorticoid response element (GRE), and binds as a dimer in head-to-head orientation with mid-nanomolar affinity (4,12–18). [...] The consensus DNA glucocorticoid response element (GRE) is comprised of two half-sites (AGAACA) separated by a three base-pair spacer (13,15,60,61)."[8]

The full fifteen nucleotide sequence AGAACANNNTGTTCT doesn't occur in any promoter for A1BG. While the TGTTCT portion was studied as part of "Androgen response elements"[9] the other portion AGAACA which is the complement inverse of TGTTCT was looked at as part of "Androgen response element2 (Kouhpayeh)".

The consensus sequence in the direction of transcription on the template strand is GAACT.[1]

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 13 2 6.5 6.5 ± 2.5 (--9,+-4)
Randoms UTR arbitrary negative 10 10 1 1.25 ± 0.25
Randoms UTR alternate negative 15 10 1.5 1.25 ± 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 2 2 1 1
Randoms Core arbitrary positive 1 10 0.1 0.05
Randoms Core alternate positive 0 10 0 0.05
Reals Proximal negative 1 2 0.5 0.5
Randoms Proximal arbitrary negative 1 10 0.1 0.05
Randoms Proximal alternate negative 0 10 0 0.05
Reals Proximal positive 2 2 1 1
Randoms Proximal arbitrary positive 3 10 0.3 0.2
Randoms Proximal alternate positive 1 10 0.1 0.2
Reals Distal negative 10 2 5 5 ± 1 (--6,+-4)
Randoms Distal arbitrary negative 23 10 2.3 2.45 ± 0.15
Randoms Distal alternate negative 26 10 2.6 2.45 ± 0.15
Reals Distal positive 7 2 3.5 3.5 ± 0.5 (-+4,++3)
Randoms Distal arbitrary positive 35 10 3.5 3.4 ± 0.1
Randoms Distal alternate positive 33 10 3.3 3.4 ± 0.1

Comparison:

The occurrences of real GAAC UTRs, cores, proximals and negative distals are greater than the randoms, positive distals are outside the randoms. This suggests that the real GAACs 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 1.5 Upinder Singh, Joshua B. Rogers (August 21, 1998). "The Novel Core Promoter Element GAAC in the hgl5 Gene of Entamoeba histolytica Is Able to Direct a Transcription Start Site Independent of TATA or Initiator Regions". The Journal of Biological Chemistry. 273 (34): 21663–8. doi:10.1074/jbc.273.34.21663. Retrieved 2013-02-13.
  2. "genetics". San Francisco, California: Wikimedia Foundation, Inc. April 16, 2014. Retrieved 2014-05-07.
  3. 3.0 3.1 Tamar Juven-Gershon, Jer-Yuan Hsu, Joshua W. M. Theisen, and James T. Kadonaga (June 2008). "The RNA Polymerase II Core Promoter – the Gateway to Transcription". Current Opinion in Cell Biology. 20 (3): 253–9. doi:10.1016/j.ceb.2008.03.003. Retrieved 2013-02-13.
  4. Serge Saxonov, Paul Berg, and Douglas L. Brutlag (January 31, 2006). "A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters". Proceedings of the National Academy of Sciences USA. 103 (5): 1412–7. doi:10.1073/pnas.0510310103. Retrieved 2013-02-13.
  5. 5.0 5.1 5.2 5.3 5.4 Catherine Terraz, Gaelle Brideau, Pierre Ronco and Jérôme Rossert (May 24, 2002). "A Combination of cis-Acting Elements Is Required to Activate the Pro-α1(I) Collagen Promoter in Tendon Fibroblasts of Transgenic Mice". The Journal of Biological Chemistry. 277 (21): 19019–26. doi:10.1074/jbc.M200125200. Retrieved 2013-02-13.
  6. Stephen Wilson; Jianfei Qi; Fabian V. Filipp (14 September 2016). "Refinement of the androgen response element based on ChIP-Seq in androgen-insensitive and androgen-responsive prostate cancer cell lines". Scientific Reports. 6: 32611. doi:10.1038/srep32611. Retrieved 3 October 2020.
  7. Matthew J. Rossi, William K.M. Lai and B. Franklin Pugh (21 March 2018). "Genome-wide determinants of sequence-specific DNA binding of general regulatory factors". Genome Research. 28: 497–508. doi:10.1101/gr.229518.117. PMID 29563167. Retrieved 31 August 2020.
  8. Nicholas V Parsonnet, Nickolaus C Lammer, Zachariah E Holmes, Robert T Batey, Deborah S Wuttke (5 September 2019). "The glucocorticoid receptor DNA-binding domain recognizes RNA hairpin structures with high affinity". Nucleic Acids Research. 47 (15): 8180–8192. doi:10.1093/nar/gkz486. PMID 31147715. Retrieved 28 August 2020.
  9. S Kouhpayeh, AR Einizadeh, Z Hejazi, M Boshtam, L Shariati, M Mirian, L Darzi, M Sojoudi, H Khanahmad and A Rezaei (1 July 2016). "Antiproliferative effect of a synthetic aptamer mimicking androgen response elements in the LNCaP cell line" (PDF). Cancer Gene Therapy. 23: 254–257. doi:10.1038/cgt.2016.26. Retrieved 3 October 2020.

Further reading

External links