Activating transcription factor gene transcriptions

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

Activating transcription factor (ATF) is a group of bZIP transcription factors, which act as homodimers or heterodimers with a range of other bZIP factors.[1] First, they have been described as members of the CREB/ATF family,[2] whereas it turned out later that some of them might be more similar to AP-1-like factors such as c-Jun or c-Fos.[3] Some of these ATFs, such as ATF3, ATF4, and ATF6 are known to play a role in stress responses.[4] Another example of ATF function would be ATFx that can suppress apoptosis.[5]

"ATF4 is known to regulate transcription by formation of the dimer complexes with the transcription factors of AP-1, Jun and C/EBP (CCAAT-enhancer binding protein) families (Horiguchi et al., 2012; Kilberg et al., 2009). The dimers bind to hybrid C/EBP-ATF responsive elements (CARE), consisting of two half-sites required for binding of C/EBP and ATF family proteins, respectively (Kilberg et al., 2009). By scanning ADM2 promoter region, we did not find potential ATF4 binding sites at reasonable distances upstream of the transcription start site. However a suitable candidate for ATF4-response element (GTTGCATCA corresponding to the consensus XTTXCATCA (Kilberg et al., 2009)) was found at a distance of 30 bp downstream from the ADM2 translation start codon."[6]

Human genes

Main article: Human genes

Genes include ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, ATF7, ATFx.

Gene ID: 466 is ATF1 activating transcription factor 1 on 12q13.12: "This gene encodes an activating transcription factor, which belongs to the ATF subfamily and bZIP (basic-region leucine zipper) family. It influences cellular physiologic processes by regulating the expression of downstream target genes, which are related to growth, survival, and other cellular activities. This protein is phosphorylated at serine 63 in its kinase-inducible domain by serine/threonine kinases, cAMP-dependent protein kinase A, calmodulin-dependent protein kinase I/II, mitogen- and stress-activated protein kinase and cyclin-dependent kinase 3 (cdk-3). Its phosphorylation enhances its transactivation and transcriptional activities, and enhances cell transformation. Fusion of this gene and FUS on chromosome 16 or EWSR1 on chromosome 22 induced by translocation generates chimeric proteins in angiomatoid fibrous histiocytoma and clear cell sarcoma. This gene has a pseudogene on chromosome 6."[7]

Consensus sequences

Main article: Consensus sequence gene transcriptions

"The ATF4 binding consensus sequence has been reported as (G/A/C)TT(G/A/T)C(G/A)TCA (38), which matches the ChIP-seq data."[8]

Combined consensus sequences are XTTXCATCA (where X = G, A or T), TTTTCATCA, and (G/A/C)TT(G/A/T)C(G/A)TCA to produce 5'-NTT(A/G/T)C(A/G)TCA-3'.

Hypotheses

Main article: Hypotheses
  1. A1BG has no Activating transcription factor in either promoter.
  2. A1BG is not transcribed by an Activating transcription factor.
  3. Activating transcription factors do not participate in the transcription of A1BG.

Samplings

Main articles: Model samplings and Samplings

Activating transcription factor samplings (Burton)

For the Basic programs testing consensus sequence 5'-(A/C/G)TT(A/G/T)C(A/G)TCA-3' (starting with SuccessablesATF.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 5'-(A/C/G)TT(A/G/T)C(A/G)TCA-3', 0.
  2. negative strand, positive direction, looking for 5'-(A/C/G)TT(A/G/T)C(A/G)TCA-3', 2, 5'-CTTGCGTCA-3' at 2423, 5'-CTTTCGTCA-3' at 1184.
  3. positive strand, negative direction, looking for 5'-(A/C/G)TT(A/G/T)C(A/G)TCA-3', 1, 5'-ATTTCATCA-3' at 2888.
  4. positive strand, positive direction, looking for 5'-(A/C/G)TT(A/G/T)C(A/G)TCA-3', 0.
  5. complement, negative strand, negative direction is SuccessablesATFc--.bas, looking for 5'-(C/G/T)AA(A/C/T)G(C/T)AGT-3', 1, 5'-TAAAGTAGT-3' at 2888.
  6. complement, negative strand, positive direction is SuccessablesATFc-+.bas, looking for 5'-(C/G/T)AA(A/C/T)G(C/T)AGT-3', 0.
  7. complement, positive strand, negative direction is SuccessablesATFc+-.bas, looking for 5'-(C/G/T)AA(A/C/T)G(C/T)AGT-3', 0.
  8. complement, positive strand, positive direction is SuccessablesATFc++.bas, looking for 5'-(C/G/T)AA(A/C/T)G(C/T)AGT-3', 2, 5'-GAACGCAGT-3' at 2423, 5'-GAAAGCAGT-3' at 1184.
  9. inverse complement, negative strand, negative direction is SuccessablesATFci--.bas, looking for 5'-TGA(C/T)G(A/C/T)AA(C/G/T)-3', 0.
  10. inverse complement, negative strand, positive direction is SuccessablesATFci-+.bas, looking for 5'-TGA(C/T)G(A/C/T)AA(C/G/T)-3', 1, 5'-TGATGAAAC-3' at 2147.
  11. inverse complement, positive strand, negative direction is SuccessablesATFci+-.bas, looking for 5'-TGA(C/T)G(A/C/T)AA(C/G/T)-3', 1, 5'-TGACGAAAC-3' at 313.
  12. inverse complement, positive strand, positive direction is SuccessablesATFci++.bas, looking for 5'-TGA(C/T)G(A/C/T)AA(C/G/T)-3', 1, 5'-TGACGTAAG-3' at 2207.
  13. inverse negative strand, negative direction is SuccessablesATFi--.bas, looking for 5'-ACT(A/G)C(A/G/T)TT(A/C/G)-3', 1, 5'-ACTGCTTTG-3' at 313.
  14. inverse negative strand, positive direction is SuccessablesATFi-+.bas, looking for 5'-ACT(A/G)C(A/G/T)TT(A/C/G)-3', 1, 5'-ACTGCATTC-3' at 2207.
  15. inverse positive strand, negative direction is SuccessablesATFi+-.bas, looking for 5'-ACT(A/G)C(A/G/T)TT(A/C/G)-3', 0.
  16. inverse positive strand, positive direction is SuccessablesATFi++.bas, looking for 5'-ACT(A/G)C(A/G/T)TT(A/C/G)-3', 1, 5'-ACTACTTTG-3' at 2147.

Activating transcription factor core promoters

Main article: Core promoter gene transcriptions

Activating transcription factor proximal promoters

Main article: Proximal promoter gene transcriptions

Activating transcription factor distal promoters

Main article: Distal promoter gene transcriptions

Positive strand, negative direction: 5'-ATTTCATCA-3' at 2888, 5'-TGACGAAAC-3' at 313 and complement.

Negative strand, positive direction: 5'-CTTGCGTCA-3' at 2423, 5'-TGACGTAAG-3' at 2207, 5'-TGATGAAAC-3' at 2147, 5'-CTTTCGTCA-3' at 1184 and complements.

Activating transcription factor samplings (Kilberg)

Copying the consensus for the ATF4: 5'-TTTTCA-3', 5'-CTTTCGTCA-3', or 5'-GTTTCA-3' 5'-GTTTCATC-3' 5'-ATTTCAT-3' (where X = G, A or T) and putting the sequence in "⌘F" finds no, no, no, no, no locations between ZSCAN22 and A1BG and no, one, no, no no, no locations between ZNF497 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence 5'-AAAAAAAA-3' (starting with SuccessablesAAA.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 SuccessablesAAA--.bas, looking for 5'-AAAAAAAA-3', 0.
  2. negative strand in the positive direction (from ZNF497 to A1BG) is SuccessablesAAA-+.bas, looking for 5'-AAAAAAAA-3', 0.
  3. positive strand, negative direction is SuccessablesAAA+-.bas, looking for 5'-AAAAAAAA-3', 0.
  4. positive strand, positive direction is SuccessablesAAA++.bas, looking for 5'-AAAAAAAA-3', 0.
  5. complement, negative strand, negative direction is SuccessablesAAAc--.bas, looking for 5'-TTTTTTTT-3', 0.
  6. complement, negative strand, positive direction is SuccessablesAAAc-+.bas, looking for 5'-TTTTTTTT-3', 0.
  7. complement, positive strand, negative direction is SuccessablesAAAc+-.bas, looking for 5'-TTTTTTTT-3', 0.
  8. complement, positive strand, positive direction is SuccessablesAAAc++.bas, looking for 5'-TTTTTTTT-3', 0.
  9. inverse complement, negative strand, negative direction is SuccessablesAAAci--.bas, looking for 5'-TTTTTTTT-3', 0.
  10. inverse complement, negative strand, positive direction is SuccessablesAAAci-+.bas, looking for 5'-TTTTTTTT-3', 0.
  11. inverse complement, positive strand, negative direction is SuccessablesAAAci+-.bas, looking for 5'-TTTTTTTT-3', 0.
  12. inverse complement, positive strand, positive direction is SuccessablesAAAci++.bas, looking for 5'-TTTTTTTT-3', 0.
  13. inverse negative strand, negative direction is SuccessablesAAAi--.bas, looking for 5'-AAAAAAAA-3', 0.
  14. inverse negative strand, positive direction is SuccessablesAAAi-+.bas, looking for 5'-AAAAAAAA-3', 0.
  15. inverse positive strand, negative direction is SuccessablesAAAi+-.bas, looking for 5'-AAAAAAAA-3', 0.
  16. inverse positive strand, positive direction is SuccessablesAAAi++.bas, looking for 5'-AAAAAAAA-3', 0.

Acknowledgements

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

See also

References

  1. ↑ van Dam H, Castellazzi M (2001). "Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis". Oncogene. 20 (19): 2453–64. doi:10.1038/sj.onc.1204239. PMID 11402340.
  2. ↑ Karin M1, Smeal T (1992). "Control of transcription factors by signal transduction pathways: the beginning of the end". Trends Biochem Sci. 17 (10): 418–22. doi:10.1016/0968-0004(92)90012-x. PMID 1455510.
  3. ↑ "Classification of Human Transcription Factors (TFClass)".
  4. ↑ Hai, Tsonwin; Hartman, Matthew G. (2001-07-25). "The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis". Gene. 273 (1): 1–11. doi:10.1016/S0378-1119(01)00551-0. ISSN 0378-1119. PMID 11483355.
  5. ↑ Green, M. R.; Persengiev, S. P. (2003-06-01). "The role of ATF/CREB family members in cell growth, survival and apoptosis". Apoptosis. 8 (3): 225–228. doi:10.1023/A:1023633704132. PMID 12766482.
  6. ↑ Irina E. Kovaleva, Alisa A. Garaeva, Peter M. Chumakov, Alexandra G. Evstafieva (17 June 2016). "Intermedin/adrenomedullin 2 is a stress-inducible gene controlled by activating transcription factor 4" (PDF). Gene. 590: 177–185. doi:10.1016/j.gene.2016.06.037. Retrieved 28 October 2020.
  7. ↑ RefSeq (August 2010). "ATF1 activating transcription factor 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 24 October 2020.
  8. ↑ Thomas D. Burton, Anthony O. Fedele, Jianling Xie, Lauren Sandeman and Christopher G. Proud (22 May 2020). "The gene for the lysosomal protein LAMP3 is a direct target of the transcription factor ATF4" (PDF). Journal of Biological Chemistry. 295 (21): 7418. doi:10.1074/jbc.RA119.011864. PMID 32312748 Check |pmid= value (help). Retrieved 5 September 2020.

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