Abf1 regulatory factor gene transcriptions

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

Human genes

GeneID: ID: 6777 is STAT5B signal transducer and activator of transcription 5B (aka STAT5). "The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein mediates the signal transduction triggered by various cell ligands, such as IL2, IL4, CSF1, and different growth hormones. It has been shown to be involved in diverse biological processes, such as TCR signaling, apoptosis, adult mammary gland development, and sexual dimorphism of liver gene expression. This gene was found to fuse to retinoic acid receptor-alpha (RARA) gene in a small subset of acute promyelocytic leukemias (APLL). The dysregulation of the signaling pathways mediated by this protein may be the cause of the APLL."[1]

  1. NP_036580.2 signal transducer and activator of transcription 5B.

Gene ID: 9242 is MSC musculin on 8q13.3 aka ABF1; MYOR; ABF-1; bHLHa22: "The protein encoded by this gene is a transcriptional repressor capable of binding an E-box element either as a homodimer or as a heterodimer with E2A in vitro. The encoded protein also forms heterodimers with E2A proteins in vivo. This protein is capable of inhibiting the transactivation capability of E47, an E2A protein, in mammalian cells. This gene is a downstream target of the B-cell receptor signal transduction pathway."[2]

Gene ID: 50616 is IL22 interleukin 22 on 12q15 aka TIFa; IL-21; IL-22; ILTIF; IL-TIF; IL-D110; zcyto18; TIFIL-23: "This gene is a member of the IL10 family of cytokines that mediate cellular inflammatory responses. The encoded protein functions in antimicrobial defense at mucosal surfaces and in tissue repair. This protein also has pro-inflammatory properties and plays a role in in the pathogenesis of several intestinal diseases. The encoded protein is a crucial cytokine that regulates host immunity in infectious diseases, including COVID-19 (disease caused by SARS-CoV-2)."[3]

"Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity."[3]

"Note: This gene (GeneID: 50616) was identified as IL-21 or IL-TIF in PMID: 10954742. The official symbol for this gene is now IL22. [19 May 2011]"[3]

Gene expressions

"Musculin (MSC), a helix-loop-helix transcription factor upregulates the PPP2R2B, a regulatory member of the PP2A enzyme resulting in the reduced phosphorylation of STAT5B Ser-193 upon IL-2 triggering in human Th17 cells [51]. Thus, Musculin leads to higher levels of PPP2R2B and impaired induction of IL-2-dependent target genes, inhibiting Th17 response to IL-2 signaling by restraining STAT5B activity [51]."[4]

Consensus sequences

Specific "sequences considered as exact Abf1 motif occurrences": CGTNNNNNACGA(C/T), CGTNNNNNA(C/T)GAC, CGTNNNNNA(C/T)GA(C/T), CGTNNNNN(A/G)(C/T)GA(C/T) (Abfm).[5]

Hypotheses

  1. A1BG has no Abf1 regulatory factors in either promoter.
  2. A1BG is not transcribed by an Abf1 regulatory factor.
  3. Abf1 regulatory factor does not participate in the transcription of A1BG.

Abf1 samplings

Copying a consensus Abf1 regulatory factor: 5'-CGTCCTCTACG-3' and putting the sequence in "⌘F" locates none between ZSCAN22 to A1BG direction, and none between ZNF497 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence 5'-CGTNNNNNACGAT-3' (starting with SuccessablesAbf1.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 (from ZSCAN22 to A1BG) is SuccessablesAbf1--.bas, looking for 5'-CGTNNNNNACGAT-3', 0.
  2. negative strand in the positive direction (from ZNF497 to A1BG) is SuccessablesAbf1-+.bas, looking for 5'-CGTNNNNNACGAT-3', 0.
  3. positive strand, negative direction is SuccessablesAbf1+-.bas, looking for 5'-CGTNNNNNACGAT-3', 0.
  4. positive strand, positive direction is SuccessablesAbf1++.bas, looking for 5'-CGTNNNNNACGAT-3', 0.
  5. complement, negative strand, negative direction is SuccessablesAbf1c--.bas, looking for 5'-GCANNNNNTGCTA-3', 0.
  6. complement, negative strand, positive direction is SuccessablesAbf1c-+.bas, looking for 5'-GCANNNNNTGCTA-3', 0.
  7. complement, positive strand, negative direction is SuccessablesAbf1c+-.bas, looking for 5'-GCANNNNNTGCTA-3', 0.
  8. complement, positive strand, positive direction is SuccessablesAbf1c++.bas, looking for 5'-GCANNNNNTGCTA-3', 0.
  9. inverse complement, negative strand, negative direction is SuccessablesAbf1ci--.bas, looking for 5'-ATCGTNNNNNACG-3', 0.
  10. inverse complement, negative strand, positive direction is SuccessablesAbf1ci-+.bas, looking for 5'-ATCGTNNNNNACG-3', 0.
  11. inverse complement, positive strand, negative direction is SuccessablesAbf1ci+-.bas, looking for 5'-ATCGTNNNNNACG-3', 0.
  12. inverse complement, positive strand, positive direction is SuccessablesAbf1ci++.bas, looking for 5'-ATCGTNNNNNACG-3', 0.
  13. inverse negative strand, negative direction is SuccessablesAbf1i--.bas, looking for 5'-TAGCANNNNNTGC-3', 0.
  14. inverse negative strand, positive direction is SuccessablesAbf1i-+.bas, looking for 5'-TAGCANNNNNTGC-3', 0.
  15. inverse positive strand, negative direction is SuccessablesAbf1i+-.bas, looking for 5'-TAGCANNNNNTGC-3', 0.
  16. inverse positive strand, positive direction is SuccessablesAbf1i++.bas, looking for 5'-TAGCANNNNNTGC-3', 0.

For the Basic programs testing consensus sequence CGTNNNNN(A/G)(C/T)GA(C/T) (starting with SuccessablesAbfm.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 is SuccessablesAbfm--.bas, looking for 5'-CGTNNNNN(A/G)(C/T)GA(C/T)-3', 0.
  2. negative strand, positive direction is SuccessablesAbfm-+.bas, looking for 5'-CGTNNNNN(A/G)(C/T)GA(C/T)-3', 0.
  3. positive strand, negative direction is SuccessablesAbfm+-.bas, looking for 5'-CGTNNNNN(A/G)(C/T)GA(C/T)-3', 1, 5'-CGTTCTTTATGAT-3' at 352.
  4. positive strand, positive direction is SuccessablesAbfm++.bas, looking for 5'-CGTNNNNN(A/G)(C/T)GA(C/T)-3', 2, 5'-CGTTCGGTGTGAC-3' at 346, 5'-CGTCACCGGTGAC-3' at 2073.
  5. complement, negative strand, negative direction is SuccessablesAbfmc--.bas, looking for 5'-GCANNNNN(C/T)(A/G)CT(A/G)-3', 1, 5'-GCAAGAAATACTA-3' at 352.
  6. complement, negative strand, positive direction is SuccessablesAbfmc-+.bas, looking for 5'-GCANNNNN(C/T)(A/G)CT(A/G)-3', 2, 5'-GCAAGCCACACTG-3' at 346, 5'-GCAGTGGCCACTG-3' at 2073.
  7. complement, positive strand, negative direction is SuccessablesAbfmc+-.bas, looking for 5'-GCANNNNN(C/T)(A/G)CT(A/G)-3', 0.
  8. complement, positive strand, positive direction is SuccessablesAbfmc++.bas, looking for 5'-GCANNNNN(C/T)(A/G)CT(A/G)-3', 0.
  9. inverse complement, negative strand, negative direction is SuccessablesAbfmci--.bas, looking for 5'-(A/G)TC(A/G)(C/T)NNNNNACG-3', 0.
  10. inverse complement, negative strand, positive direction is SuccessablesAbfmci-+.bas, looking for 5'-(A/G)TC(A/G)(C/T)NNNNNACG-3', 0.
  11. inverse complement, positive strand, negative direction is SuccessablesAbfmci+-.bas, looking for 5'-(A/G)TC(A/G)(C/T)NNNNNACG-3', 0.
  12. inverse complement, positive strand, positive direction is SuccessablesAbfmci++.bas, looking for 5'-(A/G)TC(A/G)(C/T)NNNNNACG-3', 0.
  13. inverse negative strand, negative direction is SuccessablesAbfmi--.bas, looking for 5'-(C/T)AG(C/T)(A/G)NNNNNTGC-3', 0.
  14. inverse negative strand, positive direction is SuccessablesAbfmi-+.bas, looking for 5'-(C/T)AG(C/T)(A/G)NNNNNTGC-3', 0.
  15. inverse positive strand, negative direction is SuccessablesAbfmi+-.bas, looking for 5'-(C/T)AG(C/T)(A/G)NNNNNTGC-3', 0.
  16. inverse positive strand, positive direction is SuccessablesAbfmi++.bas, looking for 5'-(C/T)AG(C/T)(A/G)NNNNNTGC-3', 0.

Abfm negative direction (2596-1) distal promoters

  1. Positive strand, negative direction: CGTTCTTTATGAT at 352.

Abfm positive direction (4050-1) distal promoters

  1. Positive strand, positive direction: CGTCACCGGTGAC at 2073, CGTTCGGTGTGAC at 346.

Abfm random dataset samplings

  1. Abfmr0: 0.
  2. Abfmr1: 0.
  3. Abfmr2: 0.
  4. Abfmr3: 1, CGTGTAGTGTGAC at 2207.
  5. Abfmr4: 0.
  6. Abfmr5: 0.
  7. Abfmr6: 1, CGTGTCATGTGAC at 1344.
  8. Abfmr7: 0.
  9. Abfmr8: 0.
  10. Abfmr9: 0.
  11. Abfmr0ci: 1, GTCATATCGTACG at 3968.
  12. Abfmr1ci: 0.
  13. Abfmr2ci: 1, ATCGCATTAAACG at 2757.
  14. Abfmr3ci: 0.
  15. Abfmr4ci: 0.
  16. Abfmr5ci: 0.
  17. Abfmr6ci: 0.
  18. Abfmr7ci: 0.
  19. Abfmr8ci: 0.
  20. Abfmr9ci: 0.

Abfmr arbitrary (evens) (4560-2846) UTRs

  1. Abfmr0ci: GTCATATCGTACG at 3968.

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

  1. Abfmr2ci: ATCGCATTAAACG at 2757.

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

  1. Abfmr6: CGTGTCATGTGAC at 1344.

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

  1. Abfmr3: CGTGTAGTGTGAC at 2207.

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

  1. Abfmr3: CGTGTAGTGTGAC at 2207.

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

  1. Abfmr6: CGTGTCATGTGAC at 1344.
  2. Abfmr0ci: GTCATATCGTACG at 3968.
  3. Abfmr2ci: ATCGCATTAAACG at 2757.

Discussion

The general consensus sequence for Abfm CGTNNNNN(A/G)(C/T)GA(C/T) occurs on both sides of A1BG but only in the distal promoters. Random datasets, even numbered arbitrarily assigned to the negative direction and odd numbered assigned to the positive direction yielded a sequence in the UTR, core promoter and distal promoter for the negative direction and a sequence in the distal promoter for the positive direction. The real consensus sequence yielded only three results: one in the negative direction and two in the positive, all in the distal promoters. The random sequences (four total) occurred in the UTR, proximal promoter and distal promoter for the negative direction and one in the distal promoter for the positive direction. While the differences between real and random are small (three vs. four), (all distal vs. UTR, proximal and two distal), they are likely significant as the random datasets (10) should have encompassed the real (2, each side of A1BG) but this did not occur.

Abfm analysis and results

Specific "sequences considered as exact Abf1 motif occurrences": CGTNNNNNACGA(C/T), CGTNNNNNA(C/T)GAC, CGTNNNNNA(C/T)GA(C/T), CGTNNNNN(A/G)(C/T)GA(C/T) (Abfm).[5]

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 0 2 0 0
Randoms UTR arbitrary negative 1 10 0.1 0.05 ± 0.05
Randoms UTR alternate negative 0 10 0 0.05 ± 0.05
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
Randoms Core alternate positive 0 10 0 0
Reals Proximal negative 0 2 0 0
Randoms Proximal arbitrary negative 1 10 0.1 0.05 ± 0.05
Randoms Proximal alternate negative 0 10 0 0.05 ± 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 1 2 0.5 0.5 ± 0.5 (--0,+-1)
Randoms Distal arbitrary negative 1 10 0.1 0.1
Randoms Distal alternate negative 1 10 0.1 0.1
Reals Distal positive 2 2 1 1 ± 1 (-+0,++2)
Randoms Distal arbitrary positive 1 10 0.1 0.2
Randoms Distal alternate positive 3 10 0.3 0.2

Comparison:

The occurrences of real Abfms are greater than the randoms. This suggests that the real Abfms are likely active or activable.

B-cell receptor signal transduction pathway

Acknowledgements

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

See also

References

  1. RefSeq (July 2008). STAT5B signal transducer and activator of transcription 5B [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 14 November 2018.
  2. RefSeq (July 2008). "MSC musculin [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 10 October 2020.
  3. 3.0 3.1 3.2 RefSeq (December 2021). "IL22 interleukin 22 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 29 September 2021.
  4. Suyasha Roy and Lalit Batra (17 May 2023). "Protein Phosphatase 2A: Role in T Cells and Diseases". Journal of Immunology Research. 2023: 4522053. doi:10.1155/2023/4522053. PMID 37234102 Check |pmid= value (help). Retrieved 29 September 2023.
  5. 5.0 5.1 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.

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