Γ-interferon activated sequence gene transcriptions

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

"To ascertain whether one or both of these two ALS-GAS sites were functionally important for GH stimulation of ALS promoter activity, plasmids containing block mutations of either ALS-GAS1 [...] or ALS-GAS2 [...] were prepared in the context of the luciferase construct retaining full responsiveness to GH [...], and transfected into H4-II-E cells [...]. Mutation of the ALS-GAS1 element abolished the ability of the promoter to respond to GH [...]; mutation of the ALS-GAS2 element was without effect. Thus, an intact ALS-GAS1 element is necessary for GH stimulation of ALS promoter activity."[1]

Human genes

Main article: Human genes

Interactions

Main article: Interaction gene transcriptions

Consensus sequences

Main article: Consensus sequence gene transcriptions

"Computer analysis of the nt −653 to nt −483 region identified two sites that resemble the [γ-interferon activated sequence] GAS consensus sequence, TTNCNNNAA (19). Similar GAS-like sites have been shown to mediate the effects of various cytokines, including [growth hormone] GH, on the transcription of other genes (19, 20). The first site, TTCCTAGAA (ALS-GAS1), is located between nt −633 and nt −625; the second site, TTAGACAAA (ALS-GAS2), is located between nt −553 and nt −545."[1]

"The GAS element is a palindromic sequence [consensus: TTCN(2–4)GAA] that binds all STATs, except for STAT2. Thus, STAT1 homodimers bind to an element with canonical N = 3 spacing (39). To date, many GAS-containing STAT1-target genes have been identified (40), including guanylate-binding protein (GBP), SOCS1, IRF1, and IRF8."[2]

"Studies of the GBP gene, which is inducible by both IFNγ and IFNα/β, has led to the identification of the IFNγ activation site (GAS, consensus sequence: TTCCNGGAA (40) [...]), in addition to an ISRE (104, 105). Subsequently, GAS was shown to be involved in the IFN-II-mediated transcriptional activation of several other genes and predominantly localized in their proximal promoters [...]. In the GBP gene, an ISRE was also found juxtaposed to the GAS, and both elements clearly contributed to both IFN-I and IFN-II responses (105, 106). Additional genes, stimulating cooperation of ISGF3 and GAF on ISRE and GAS composites have since been identified (40, 107) [...]. [...] In addition, binding modes exist in which multiple [γ-activated factor] GAF complexes can be recruited to adjacent GAS sites (13, 108). Similar cooperative DNA-binding has been described for ISGF3 (109)."[2]

Hypotheses

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

Γ-interferon activated sequence samplings

Comparison of GAS-Like Elements Shown to Mediate the Effect of GH on Chromosomal Genes:[1]
Name of element Sequence Preferred STAT Gene and reference
Spi-GLE1 TTC TGA GAA STAT5 Rat Spi 2.1 (27)
INS-GLE TTC TGG GAA STAT5 Rat insulin (29)
CYPGHRE TTC CTG GAA STAT5 Hamster CYP3A10/6β (30)
ALS-GAS1 TTC CTA GAA STAT5 Mouse ALS (this study)
SIE TTC CCG TAA STAT1 and 3 Rat c-fos (22,57–59)
m67 TTC CCG TCA STAT1 and 3 Optimized c-fos SIE (22)

Copying a responsive element consensus sequence TTNCNNNAA and putting the sequence in "⌘F" finds none between ZNF497 and A1BG and none between ZSCAN22 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence TTNCNNNAA (starting with SuccessablesGAS.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 TTNCNNNAA, 3, TTTCTGTAA at 4509, TTTCCAAAA at 3349, TTTCGTAAA at 189.
  2. negative strand, positive direction, looking for TTNCNNNAA, 2, TTCCGGGAA at 4247, TTGCAGGAA at 2747.
  3. positive strand, negative direction, looking for TTNCNNNAA, 7, TTCCCTGAA at 3782, TTTCATCAA at 2889, TTGCTTGAA at 2380, TTGCCTGAA at 1624, TTTCAAAAA at 1385, TTACTTGAA at 1301, TTGCTTGAA at 1010.
  4. positive strand, positive direction, looking for TTNCNNNAA, 2, TTTCCGAAA at 1095, TTCCATGAA at 128.
  5. complement, negative strand, negative direction, looking for AANGNNNTT, 7, AAGGGACTT at 3782, AAAGTAGTT at 2889, AACGAACTT at 2380, AACGGACTT at 1624, AAAGTTTTT at 1385, AATGAACTT at 1301, AACGAACTT at 1010.
  6. complement, negative strand, positive direction, looking for AANGNNNTT, 2, AAAGGCTTT at 1095, AAGGTACTT at 128.
  7. complement, positive strand, negative direction, looking for AANGNNNTT, 3, AAAGACATT at 4509, AAAGGTTTT at 3349, AAAGCATTT at 189.
  8. complement, positive strand, positive direction, looking for AANGNNNTT, 2, AAGGCCCTT at 4247, AACGTCCTT at 2747.
  9. inverse complement, negative strand, negative direction, looking for TTNNNGNAA, 5, TTTCTGTAA at 4509, TTTAAGCAA at 3503, TTGAGGTAA at 1378, TTTTCGTAA at 188, TTAAAGAAA at 25, and complements.
  10. inverse complement, negative strand, positive direction, looking for TTNNNGNAA, 3, TTCCGGGAA at 4247, TTGCAGGAA at 2747, TTTTTGTAA at 2455, and complements.
  11. inverse complement, positive strand, negative direction, looking for TTNNNGNAA, 3, TTAAGGAAA at 2957, TTGGGGAAA at 2926, TTCGGGAAA at 2458, and complements.
  12. inverse complement, positive strand, positive direction, looking for TTNNNGNAA, 2, TTGTAGTAA at 4118, TTTCCGAAA at 1095, and complements.
  13. inverse negative strand, negative direction, looking for AANNNCNTT, 3, AATTCCTTT at 2957, AACCCCTTT at 2926, AAGCCCTTT at 2458.
  14. inverse negative strand, positive direction, looking for AANNNCNTT, 2, AACATCATT at 4118, AAAGGCTTT at 1095.
  15. inverse positive strand, negative direction, looking for AANNNCNTT, 5, AAAGACATT at 4509, AAATTCGTT at 3503, AACTCCATT at 1378, AAAAGCATT at 188, AATTTCTTT at 25.
  16. inverse positive strand, positive direction, looking for AANNNCNTT, 3, AAGGCCCTT at 4247, AACGTCCTT at 2747, AAAAACATT at 2455.

GAS UTRs

  1. Negative strand, negative direction: TTTCTGTAA at 4509, TTTAAGCAA at 3503, TTTCCAAAA at 3349.
  2. Positive strand, negative direction: TTCCCTGAA at 3782, TTAAGGAAA at 2957, TTGGGGAAA at 2926, TTTCATCAA at 2889.

GAS proximal promoters

  1. Negative strand, positive direction: TTCCGGGAA at 4247.
  2. Positive strand, positive direction: TTGTAGTAA at 4118.

GAS distal promoters

  1. Negative strand, negative direction: TTGAGGTAA at 1378, TTTCGTAAA at 189, TTTTCGTAA at 188, TTAAAGAAA at 25.
  2. Positive strand, negative direction: TTCGGGAAA at 2458, TTGCTTGAA at 2380, TTGCCTGAA at 1624, TTTCAAAAA at 1385, TTACTTGAA at 1301, TTGCTTGAA at 1010.


  1. Negative strand, positive direction: TTGCAGGAA at 2747, TTTTTGTAA at 2455.
  2. Positive strand, positive direction: TTTCCGAAA at 1095.

Γ-interferon activated sequence random dataset samplings

  1. GASr0: 9, TTACCTAAA at 4428, TTTCCTTAA at 4208, TTACCCGAA at 4137, TTACCGCAA at 4039, TTACCGTAA at 3782, TTTCCTTAA at 3691, TTGCACCAA at 3479, TTGCACAAA at 1787, TTACCAAAA at 194.
  2. RDr1: 0.
  3. RDr2: 0.
  4. RDr3: 0.
  5. RDr4: 0.
  6. RDr5: 0.
  7. RDr6: 0.
  8. RDr7: 0.
  9. RDr8: 0.
  10. RDr9: 0.
  11. RDr0ci: 0.
  12. RDr1ci: 0.
  13. RDr2ci: 0.
  14. RDr3ci: 0.
  15. RDr4ci: 0.
  16. RDr5ci: 0.
  17. RDr6ci: 0.
  18. RDr7ci: 0.
  19. RDr8ci: 0.
  20. RDr9ci: 0.

GASr UTRs

Main article: UTR promoter gene transcriptions
  1. GASr0: TTACCTAAA at 4428, TTTCCTTAA at 4208, TTACCCGAA at 4137, TTACCGCAA at 4039, TTACCGTAA at 3782, TTTCCTTAA at 3691, TTGCACCAA at 3479.

RDr core promoters

Main article: Core promoter gene transcriptions

RDr proximal promoters

Main article: Proximal promoter gene transcriptions

GASr distal promoters

Main article: Distal promoter gene transcriptions
  1. GASr0: TTGCACAAA at 1787, TTACCAAAA at 194.

Γ-interferon activated sequence analysis and results

Main article: Complex locus A1BG and ZNF497 § Name of elements

Response element (AAAAAA).<Author reference>

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 negative 0 10 0 0
Reals Core positive 0 2 0 0
Randoms Core positive 0 10 0 0
Reals Proximal negative 0 2 0 0
Randoms Proximal negative 0 10 0 0
Reals Proximal positive 0 2 0 0
Randoms Proximal positive 0 10 0 0
Reals Distal negative 1 2 0.5 0.5
Randoms Distal negative 1 10 0.1 0.05
Reals Distal positive 1 2 0.5 0.5
Randoms Distal positive 0 10 0 0.05

Comparison:

The occurrences of real responsive element consensus sequences are larger than the randoms. This suggests that the real responsive element consensus sequences 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 1.2 Guck T. Ooi, Kelley R. Hurst, Matthew N. Poy, Matthew M. Rechler, Yves R. Boisclair (1 May 1998). "Binding of STAT5a and STAT5b to a Single Element Resembling a γ-Interferon-Activated Sequence Mediates the Growth Hormone Induction of the Mouse Acid-Labile Subunit Promoter in Liver Cells". Molecular Endocrinology. 12 (5): 675–687. doi:10.1210/mend.12.5.0115. PMID 9605930. Retrieved 9 September 2020.
  2. ↑ 2.0 2.1 Agata Michalska, Katarzyna Blaszczyk, Joanna Wesoly and Hans A. R. Bluyssen (28 May 2018). "A Positive Feedback Amplifier Circuit That Regulates Interferon (IFN)-Stimulated Gene Expression and Controls Type I and Type II IFN Responses". Frontiers in Immunology. 9: 1135. doi:10.3389/fimmu.2018.01135. Retrieved 18 March 2021.

External links

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