Activating transcription factor gene transcriptions: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
(Created page with "{{AE}} Henry A. Hoff Activating transcription factor (ATF) is a group of bZIP transcription factors, which act as homodimers or heterodimers with a range...")
 
mNo edit summary
 
(33 intermediate revisions by the same user not shown)
Line 1: Line 1:
{{AE}} Henry A. Hoff
{{AE}} Henry A. Hoff


Activating transcription factor (ATF) is a group of [[bZIP domain|bZIP]] [[transcription factor]]s, which act as homodimers or heterodimers with a range of other bZIP factors.<ref name="van Dam">{{ cite journal |author=van Dam H, Castellazzi M |title=Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis |journal= Oncogene |volume=20 |issue=19 |pages=2453–64 |year=2001 |pmid= 11402340 |doi=10.1038/sj.onc.1204239 }}</ref> First, they have been described as members of the [[ATF/CREB|CREB/ATF]] family,<ref name="Karin">{{cite journal |author=Karin M1, Smeal T |title=Control of transcription factors by signal transduction pathways: the beginning of the end |journal= Trends Biochem Sci|volume=17 |issue=10 |pages=418–22 |year=1992 |pmid= 1455510 |doi=10.1016/0968-0004(92)90012-x}}</ref> whereas it turned out later that some of them might be more similar to [[AP-1 transcription factor|AP-1]]-like factors such as [[c-Jun]] or [[c-Fos]].<ref name="TFClass">{{ cite web | title = Classification of Human Transcription Factors (TFClass)| url = https://web.archive.org/web/20140407072323/http://tfclass.bioinf.med.uni-goettingen.de/tfclass }}</ref> In general, ATFs are known to respond to extracellular signals and this suggests an important role that they have in maintaining homeostasis. Some of these ATFs, such as ATF3, ATF4, and ATF6 are known to play a role in stress responses.<ref>{{ cite journal|date=2001-07-25|title=The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis
Activating transcription factor (ATF) is a group of [[bZIP domain|bZIP]] [[transcription factor]]s, which act as homodimers or heterodimers with a range of other bZIP factors.<ref name="van Dam">{{ cite journal |author=van Dam H, Castellazzi M |title=Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis |journal= Oncogene |volume=20 |issue=19 |pages=2453–64 |year=2001 |pmid= 11402340 |doi=10.1038/sj.onc.1204239 }}</ref> First, they have been described as members of the [[ATF/CREB|CREB/ATF]] family,<ref name="Karin">{{cite journal |author=Karin M, Smeal T |title=Control of transcription factors by signal transduction pathways: the beginning of the end
|journal= Trends Biochem Sci
|volume=17
|issue=10
|pages=418–22
|year=1992
|pmid= 1455510
|doi=10.1016/0968-0004(92)90012-x}}</ref> whereas it turned out later that some of them might be more similar to [[AP-1 transcription factor|AP-1]]-like factors such as [[c-Jun]] or [[c-Fos]].<ref name="TFClass">{{ cite web
| title = Classification of Human Transcription Factors (TFClass)
| url = https://web.archive.org/web/20140407072323/http://tfclass.bioinf.med.uni-goettingen.de/tfclass }}</ref> Some of these ATFs, such as ATF3, ATF4, and ATF6 are known to play a role in stress responses.<ref name=Hai>{{ cite journal
|date=2001-07-25
|title=The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis
|url=
|url=
|journal=Gene
|journal=Gene
Line 10: Line 21:
|pmid=11483355
|pmid=11483355
|issn=0378-1119
|issn=0378-1119
|last1=Hai|first1=Tsonwin|last2=Hartman|first2=Matthew G.}}</ref> Another example of ATF function would be ATFx that can suppress apoptosis.<ref>{{ cite journal
|last1=Hai|first1=Tsonwin|last2=Hartman|first2=Matthew G.}}</ref> Another example of ATF function would be ATFx that can suppress apoptosis.<ref name=Green>{{ cite journal
|last1=Green|first1=M. R.|last2=Persengiev|first2=S. P.
|last1=Green|first1=M. R.|last2=Persengiev|first2=S. P.
|date=2003-06-01
|date=2003-06-01
Line 21: Line 32:
|pmid=12766482 }}</ref>
|pmid=12766482 }}</ref>


Genes include [[ATF1]], [[Activating transcription factor 2|ATF2]], [[ATF3]], [[ATF4]], [[ATF5]], [[ATF6]], [[ATF7]], ATFx.
"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."<ref name=Kovaleva>{{ cite journal
|author=Irina E. Kovaleva, Alisa A. Garaeva, Peter M. Chumakov, Alexandra G. Evstafieva
|title=Intermedin/adrenomedullin 2 is a stress-inducible gene controlled by activating transcription factor 4
|journal=Gene
|date=17 June 2016
|volume=590
|issue=
|pages=177-185
|url=https://www.researchgate.net/profile/Peter_Chumakov2/publication/304249961_IntermedinAdrenomedullin_2_is_a_stress-inducible_gene_controlled_by_Activating_Transcription_Factor_4/links/5c2f3b45299bf12be3ab9075/Intermedin-Adrenomedullin-2-is-a-stress-inducible-gene-controlled-by-Activating-Transcription-Factor-4.pdf
|arxiv=
|bibcode=
|doi=10.1016/j.gene.2016.06.037
|pmid=
|accessdate=28 October 2020 }}</ref>
 
"ATF4 regulates transcription of its target genes through the formation of homodimers or heterooligomers with the transcription factors Jun, AP-1 and C/EBP<sup>38,39</sup> that bind to CARE (C/EBP-ATF) responsive elements having the consensus sequence XTTXCATCA (where X = G, A or T).<sup>39</sup> In the region from -625 to -618 bp relative to the ''SESN2'' translation start codon (from -228 to -221 bp relative to the transcription start site) we found a candidate sequence for the ATF4 binding site TTTTCATCA."<ref name=Garaeva/>


==Human genes==
==Human genes==
{{main|Human genes}}
{{main|Human genes}}
Genes include [[ATF1]], [[Activating transcription factor 2|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."<ref name=RefSeq2010>{{ cite web
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."<ref name=RefSeq2010>{{ cite web
|author=RefSeq
|author=RefSeq
Line 33: Line 61:
|url=https://www.ncbi.nlm.nih.gov/gene/2623
|url=https://www.ncbi.nlm.nih.gov/gene/2623
|accessdate=24 October 2020 }}</ref>
|accessdate=24 October 2020 }}</ref>
==Gene expressions==
{{main|Gene expressions}}
==Interactions==
{{main|Interaction gene transcriptions}}


==Consensus sequences==
==Consensus sequences==
{{main|Consensus sequence gene transcriptions}}
{{main|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."<ref name=Burton>{{ cite journal
|author=Thomas D. Burton, Anthony O. Fedele, Jianling Xie, Lauren Sandeman and Christopher G. Proud
|title=The gene for the lysosomal protein LAMP3 is a direct target of the transcription factor ATF4
|journal=Journal of Biological Chemistry
|date=22 May 2020
|volume=295
|issue=21
|pages=7418
|url=https://www.jbc.org/content/early/2020/04/20/jbc.RA119.011864.full.pdf
|arxiv=
|bibcode=
|doi=10.1074/jbc.RA119.011864
|pmid=32312748
|accessdate=5 September 2020 }}</ref>


==Binding site for==
5'-(A/G/T)TT(A/G/T)CATCA-3'<ref name=Garaeva>{{ cite journal
 
|author=Alisa A. Garaeva, Irina E. Kovaleva, Peter M. Chumakov & Alexandra G. Evstafieva
==Inverse copies==
|title=Mitochondrial dysfunction induces ''SESN2'' gene expression through Activating Transcription Factor 4
 
|journal=Cell Cycle
==Enhancer activity==
|date=15 January 2016
|volume=15
|issue=1
|pages=64-71
|url=https://www.tandfonline.com/doi/full/10.1080/15384101.2015.1120929
|arxiv=
|bibcode=
|doi=10.1080/15384101.2015.1120929
|pmid=26771712
|accessdate=5 September 2020 }}</ref>


==Promoter occurrences==
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==
==Hypotheses==
Line 57: Line 102:
# Activating transcription factors do not participate in the transcription of A1BG.
# Activating transcription factors do not participate in the transcription of A1BG.


==Samplings==
==Activating transcription factor samplings (Burton)==
{{main|Model samplings|Samplings}}
{{main|Model samplings|Samplings}}
Copying a responsive elements consensus sequence 5'-AAAAAAAA-3' and putting the sequence in "⌘F" finds none between ZNF497 and A1BG or none between ZSCAN22 and A1BG as can be found by the computer programs.
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:
# negative strand, negative direction, looking for 5'-(A/C/G)TT(A/G/T)C(A/G)TCA-3', 0.
# 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.
# 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.
# positive strand, positive direction, looking for 5'-(A/C/G)TT(A/G/T)C(A/G)TCA-3', 0.
# 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.
# 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.
# 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.
# 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.
 
===ATFB (4560-2846) UTRs===
 
# Positive strand, negative direction: ATTTCATCA at 2888.
 
===ATFB negative direction (2596-1) distal promoters===
 
# Positive strand, negative direction: TGACGAAAC at 313.
 
===ATFB positive direction (4050-1) distal promoters===
 
# Negative strand, positive direction: CTTGCGTCA at 2423, TGATGAAAC at 2147, CTTTCGTCA at 1184.
# Positive strand, positive direction: TGACGTAAG at 2207.
 
==Activating transcription factor (Burton) random dataset samplings==
 
# ATFBr0: 0.
# ATFBr1: 0.
# ATFBr2: 0.
# ATFBr3: 0.
# ATFBr4: 0.
# ATFBr5: 0.
# ATFBr6: 0.
# ATFBr7: 0.
# ATFBr8: 0.
# ATFBr9: 1, GTTTCATCA at 1242.
# ATFBr0ci: 1, TGATGAAAC at 1932.
# ATFBr1ci: 0.
# ATFBr2ci: 0.
# ATFBr3ci: 0.
# ATFBr4ci: 0.
# ATFBr5ci: 0.
# ATFBr6ci: 0.
# ATFBr7ci: 0.
# ATFBr8ci: 0.
# ATFBr9ci: 0.
 
===ATFBr arbitrary negative direction (evens) (2596-1) distal promoters===
 
# ATFBr0ci: TGATGAAAC at 1932.
 
===ATFBr alternate negative direction (odds) (2596-1) distal promoters===
 
# ATFBr9: GTTTCATCA at 1242.
 
===ATFBr arbitrary positive direction (odds) (4050-1) distal promoters===
 
# ATFBr9: GTTTCATCA at 1242.
 
===ATFBr alternate positive direction (evens) (4050-1) distal promoters===
 
# ATFBr0ci: TGATGAAAC at 1932.
 
==Activating transcription factor (Burton) analysis and results==
{{main|Complex locus A1BG and ZNF497#ATFBs}}
"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."<ref name=Burton/>
 
{|class="wikitable"
|-
! Reals or randoms !! Promoters !! direction !! Numbers !! Strands !! Occurrences !! Averages (± 0.1)
|-
| Reals || UTR || negative || 1 || 2 || 0.5 || 0.5
|-
| 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 || 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 || 0 || 10 || 0 || 0
|-
| Randoms || Proximal || alternate negative || 0 || 10 || 0 || 0
|-
| 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
|-
| Randoms || Distal || arbitrary negative || 1 || 10 || 0.1 || 0.1
|-
| Randoms || Distal || alternate negative || 1 || 10 || 0.1 || 0.1
|-
| Reals || Distal || positive || 4 || 2 || 2 || 2
|-
| Randoms || Distal || arbitrary positive || 1 || 10 || 0.1 || 0.1
|-
| Randoms || Distal || alternate positive || 1 || 10 || 0.1 || 0.1
|}
 
Comparison:
 
The occurrences of real activating transcription factor (Burton) UTRs and distals are greater than the randoms. This suggests that the real activating transcription factor (Burton)s are likely active or activable.
 
==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. Consensus sequence (Kilberg 2009): XTTXCATCA (where X = G, A or T) is 5'-(A/G/T)TT(A/G/T)CATCA-3'.
 
For the Basic programs testing consensus sequence 5'-(A/G/T)TT(A/G/T)CATCA-3' (starting with SuccessablesATFK.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:
# negative strand, negative direction, looking for 5'-(A/G/T)TT(A/G/T)CATCA-3', 0.
# negative strand, positive direction, looking for 5'-(A/G/T)TT(A/G/T)CATCA-3', 0.
# positive strand, negative direction, looking for 5'-(A/G/T)TT(A/G/T)CATCA-3', 1, 5'-ATTTCATCA-3' at 2888.
# positive strand, positive direction, looking for 5'-(A/G/T)TT(A/G/T)CATCA-3', 0.
# inverse complement, negative strand, negative direction, looking for 5'-TGATG(A/C/T)AA(A/C/T)-3', 0.
# inverse complement, negative strand, positive direction, looking for 5'-TGATG(A/C/T)AA(A/C/T)-3', 1, 5'-TGATGAAAC-3' at 2147.
# inverse complement, positive strand, negative direction, looking for 5'-TGATG(A/C/T)AA(A/C/T)-3', 0.
# inverse complement, positive strand, positive direction, looking for 5'-TGATG(A/C/T)AA(A/C/T)-3', 0.
 
===ATFK (4560-2846) UTRs===
 
# Positive strand, negative direction: ATTTCATCA at 2888.
 
===ATFK positive direction (4050-1) distal promoters===
 
# Negative strand, positive direction: TGATGAAAC at 2147.
 
==Activating transcription factor (Kilberg) random dataset samplings==
 
# ATFKr0: 0.
# ATFKr1: 0.
# ATFKr2: 0.
# ATFKr3: 0.
# ATFKr4: 0.
# ATFKr5: 0.
# ATFKr6: 0.
# ATFKr7: 0.
# ATFKr8: 0.
# ATFKr9: 1, GTTTCATCA at 1242.
# ATFKr0ci: 1, TGATGAAAC at 1932.
# ATFKr1ci: 0.
# ATFKr2ci: 0.
# ATFKr3ci: 0.
# ATFKr4ci: 0.
# ATFKr5ci: 0.
# ATFKr6ci: 0.
# ATFKr7ci: 0.
# ATFKr8ci: 0.
# ATFKr9ci: 0.
 
===ATFKr arbitrary negative direction (evens) (2596-1) distal promoters===
 
# ATFKr0ci: TGATGAAAC at 1932.
 
===ATFKr alternate negative direction (odds) (2596-1) distal promoters===
 
# ATFKr9: GTTTCATCA at 1242.
 
===ATFKr arbitrary positive direction (odds) (4050-1) distal promoters===
 
# ATFKr9: GTTTCATCA at 1242.
 
===ATFKr alternate positive direction (evens) (4050-1) distal promoters===
 
# ATFKr0ci: TGATGAAAC at 1932.
 
==Activating transcription factor (Kilberg) analysis and results==
{{main|Complex locus A1BG and ZNF497#ATFKs}}
The consensus XTTXCATCA (Kilberg ''et al''., 2009) "having the sequence XTTXCATCA (where X = G, A or T).<sup>39</sup> In the region from -625 to -618 bp relative to the ''SESN2'' translation start codon (from -228 to -221 bp relative to the transcription start site) we found a candidate sequence for the ATF4 binding site TTTTCATCA."<ref name=Garaeva/>


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:
{|class="wikitable"
# negative strand in the negative direction (from ZSCAN22 to A1BG) is SuccessablesAAA--.bas, looking for 5'-AAAAAAAA-3', 0.
|-
# negative strand in the positive direction (from ZNF497 to A1BG) is SuccessablesAAA-+.bas, looking for 5'-AAAAAAAA-3', 0.
! Reals or randoms !! Promoters !! direction !! Numbers !! Strands !! Occurrences !! Averages (± 0.1)  
# positive strand, negative direction is SuccessablesAAA+-.bas, looking for 5'-AAAAAAAA-3', 0.
|-
# positive strand, positive direction is SuccessablesAAA++.bas, looking for 5'-AAAAAAAA-3', 0.
| Reals || UTR || negative || 1 || 2 || 0.5 || 0.5
# complement, negative strand, negative direction is SuccessablesAAAc--.bas, looking for 5'-TTTTTTTT-3', 0.
|-
# complement, negative strand, positive direction is SuccessablesAAAc-+.bas, looking for 5'-TTTTTTTT-3', 0.
| Randoms || UTR || arbitrary negative || 0 || 10 || 0 || 0
# complement, positive strand, negative direction is SuccessablesAAAc+-.bas, looking for 5'-TTTTTTTT-3', 0.
|-
# complement, positive strand, positive direction is SuccessablesAAAc++.bas, looking for 5'-TTTTTTTT-3', 0.
| Randoms || UTR || alternate negative || 0 || 10 || 0 || 0
# inverse complement, negative strand, negative direction is SuccessablesAAAci--.bas, looking for 5'-TTTTTTTT-3', 0.
|-
# inverse complement, negative strand, positive direction is SuccessablesAAAci-+.bas, looking for 5'-TTTTTTTT-3', 0.
| Reals || Core || negative || 0 || 2 || 0 || 0
# inverse complement, positive strand, negative direction is SuccessablesAAAci+-.bas, looking for 5'-TTTTTTTT-3', 0.
|-
# inverse complement, positive strand, positive direction is SuccessablesAAAci++.bas, looking for 5'-TTTTTTTT-3', 0.
| Randoms || Core || arbitrary negative || 0 || 10 || 0 || 0
# inverse negative strand, negative direction is SuccessablesAAAi--.bas, looking for 5'-AAAAAAAA-3', 0.
|-
# inverse negative strand, positive direction is SuccessablesAAAi-+.bas, looking for 5'-AAAAAAAA-3', 0.
| Randoms || Core || alternate negative || 0 || 10 || 0 || 0
# inverse positive strand, negative direction is SuccessablesAAAi+-.bas, looking for 5'-AAAAAAAA-3', 0.
|-
# inverse positive strand, positive direction is SuccessablesAAAi++.bas, looking for 5'-AAAAAAAA-3', 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 || 0 || 10 || 0 || 0
|-
| Randoms || Proximal || alternate negative || 0 || 10 || 0 || 0
|-
| 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 || 0 || 2 || 0 || 0  
|-
| Randoms || Distal || arbitrary negative || 1 || 10 || 0.1 || 0.1
|-
| Randoms || Distal || alternate negative || 1 || 10 || 0.1 || 0.1
|-
| Reals || Distal || positive || 1 || 2 || 0.5 || 0.5
|-
| Randoms || Distal || arbitrary positive || 1 || 10 || 0.1 || 0.1
|-
| Randoms || Distal || alternate positive || 1 || 10 || 0.1 || 0.1
|}


===AAA core promoters===
Comparison:
{{main|Core promoter gene transcriptions}}


===AAA proximal promoters===
The occurrences of real activating transcription factor (Kilberg) UTRs and positive direction distals are greater than the randoms. This suggests that the real activating transcription factor (Kilberg)s are likely active or activable.
{{main|Proximal promoter gene transcriptions}}


===AAA distal promoters===
==Signal transduction pathways==
{{main|Distal promoter gene transcriptions}}


==Acknowledgements==
==Acknowledgements==

Latest revision as of 06:35, 8 May 2023

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]

"ATF4 regulates transcription of its target genes through the formation of homodimers or heterooligomers with the transcription factors Jun, AP-1 and C/EBP38,39 that bind to CARE (C/EBP-ATF) responsive elements having the consensus sequence XTTXCATCA (where X = G, A or T).39 In the region from -625 to -618 bp relative to the SESN2 translation start codon (from -228 to -221 bp relative to the transcription start site) we found a candidate sequence for the ATF4 binding site TTTTCATCA."[7]

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."[8]

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."[9]

5'-(A/G/T)TT(A/G/T)CATCA-3'[7]

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.

Activating transcription factor samplings (Burton)

Main articles: Model samplings and Samplings

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. 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.
  6. 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.
  7. 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.
  8. 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.

ATFB (4560-2846) UTRs

  1. Positive strand, negative direction: ATTTCATCA at 2888.

ATFB negative direction (2596-1) distal promoters

  1. Positive strand, negative direction: TGACGAAAC at 313.

ATFB positive direction (4050-1) distal promoters

  1. Negative strand, positive direction: CTTGCGTCA at 2423, TGATGAAAC at 2147, CTTTCGTCA at 1184.
  2. Positive strand, positive direction: TGACGTAAG at 2207.

Activating transcription factor (Burton) random dataset samplings

  1. ATFBr0: 0.
  2. ATFBr1: 0.
  3. ATFBr2: 0.
  4. ATFBr3: 0.
  5. ATFBr4: 0.
  6. ATFBr5: 0.
  7. ATFBr6: 0.
  8. ATFBr7: 0.
  9. ATFBr8: 0.
  10. ATFBr9: 1, GTTTCATCA at 1242.
  11. ATFBr0ci: 1, TGATGAAAC at 1932.
  12. ATFBr1ci: 0.
  13. ATFBr2ci: 0.
  14. ATFBr3ci: 0.
  15. ATFBr4ci: 0.
  16. ATFBr5ci: 0.
  17. ATFBr6ci: 0.
  18. ATFBr7ci: 0.
  19. ATFBr8ci: 0.
  20. ATFBr9ci: 0.

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

  1. ATFBr0ci: TGATGAAAC at 1932.

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

  1. ATFBr9: GTTTCATCA at 1242.

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

  1. ATFBr9: GTTTCATCA at 1242.

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

  1. ATFBr0ci: TGATGAAAC at 1932.

Activating transcription factor (Burton) analysis and results

Main article: Complex locus A1BG and ZNF497 § ATFBs

"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."[9]

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 1 2 0.5 0.5
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 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 0 10 0 0
Randoms Proximal alternate negative 0 10 0 0
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
Randoms Distal arbitrary negative 1 10 0.1 0.1
Randoms Distal alternate negative 1 10 0.1 0.1
Reals Distal positive 4 2 2 2
Randoms Distal arbitrary positive 1 10 0.1 0.1
Randoms Distal alternate positive 1 10 0.1 0.1

Comparison:

The occurrences of real activating transcription factor (Burton) UTRs and distals are greater than the randoms. This suggests that the real activating transcription factor (Burton)s are likely active or activable.

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. Consensus sequence (Kilberg 2009): XTTXCATCA (where X = G, A or T) is 5'-(A/G/T)TT(A/G/T)CATCA-3'.

For the Basic programs testing consensus sequence 5'-(A/G/T)TT(A/G/T)CATCA-3' (starting with SuccessablesATFK.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/G/T)TT(A/G/T)CATCA-3', 0.
  2. negative strand, positive direction, looking for 5'-(A/G/T)TT(A/G/T)CATCA-3', 0.
  3. positive strand, negative direction, looking for 5'-(A/G/T)TT(A/G/T)CATCA-3', 1, 5'-ATTTCATCA-3' at 2888.
  4. positive strand, positive direction, looking for 5'-(A/G/T)TT(A/G/T)CATCA-3', 0.
  5. inverse complement, negative strand, negative direction, looking for 5'-TGATG(A/C/T)AA(A/C/T)-3', 0.
  6. inverse complement, negative strand, positive direction, looking for 5'-TGATG(A/C/T)AA(A/C/T)-3', 1, 5'-TGATGAAAC-3' at 2147.
  7. inverse complement, positive strand, negative direction, looking for 5'-TGATG(A/C/T)AA(A/C/T)-3', 0.
  8. inverse complement, positive strand, positive direction, looking for 5'-TGATG(A/C/T)AA(A/C/T)-3', 0.

ATFK (4560-2846) UTRs

  1. Positive strand, negative direction: ATTTCATCA at 2888.

ATFK positive direction (4050-1) distal promoters

  1. Negative strand, positive direction: TGATGAAAC at 2147.

Activating transcription factor (Kilberg) random dataset samplings

  1. ATFKr0: 0.
  2. ATFKr1: 0.
  3. ATFKr2: 0.
  4. ATFKr3: 0.
  5. ATFKr4: 0.
  6. ATFKr5: 0.
  7. ATFKr6: 0.
  8. ATFKr7: 0.
  9. ATFKr8: 0.
  10. ATFKr9: 1, GTTTCATCA at 1242.
  11. ATFKr0ci: 1, TGATGAAAC at 1932.
  12. ATFKr1ci: 0.
  13. ATFKr2ci: 0.
  14. ATFKr3ci: 0.
  15. ATFKr4ci: 0.
  16. ATFKr5ci: 0.
  17. ATFKr6ci: 0.
  18. ATFKr7ci: 0.
  19. ATFKr8ci: 0.
  20. ATFKr9ci: 0.

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

  1. ATFKr0ci: TGATGAAAC at 1932.

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

  1. ATFKr9: GTTTCATCA at 1242.

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

  1. ATFKr9: GTTTCATCA at 1242.

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

  1. ATFKr0ci: TGATGAAAC at 1932.

Activating transcription factor (Kilberg) analysis and results

Main article: Complex locus A1BG and ZNF497 § ATFKs

The consensus XTTXCATCA (Kilberg et al., 2009) "having the sequence XTTXCATCA (where X = G, A or T).39 In the region from -625 to -618 bp relative to the SESN2 translation start codon (from -228 to -221 bp relative to the transcription start site) we found a candidate sequence for the ATF4 binding site TTTTCATCA."[7]

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 1 2 0.5 0.5
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 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 0 10 0 0
Randoms Proximal alternate negative 0 10 0 0
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 0 2 0 0
Randoms Distal arbitrary negative 1 10 0.1 0.1
Randoms Distal alternate negative 1 10 0.1 0.1
Reals Distal positive 1 2 0.5 0.5
Randoms Distal arbitrary positive 1 10 0.1 0.1
Randoms Distal alternate positive 1 10 0.1 0.1

Comparison:

The occurrences of real activating transcription factor (Kilberg) UTRs and positive direction distals are greater than the randoms. This suggests that the real activating transcription factor (Kilberg)s are likely active or activable.

Signal transduction pathways

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 M, 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. ↑ 7.0 7.1 7.2 Alisa A. Garaeva, Irina E. Kovaleva, Peter M. Chumakov & Alexandra G. Evstafieva (15 January 2016). "Mitochondrial dysfunction induces SESN2 gene expression through Activating Transcription Factor 4". Cell Cycle. 15 (1): 64–71. doi:10.1080/15384101.2015.1120929. PMID 26771712. Retrieved 5 September 2020.
  8. ↑ 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.
  9. ↑ 9.0 9.1 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.

External links

Retrieved from "https://www.wikidoc.org/index.php?title=Activating_transcription_factor_gene_transcriptions&oldid=1733981"