Affinage

ATF7

Cyclic AMP-dependent transcription factor ATF-7 · UniProt P17544

Length
483 aa
Mass
51.8 kDa
Annotated
2026-06-09
53 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATF7 (ATFa) is a stress-responsive bZIP transcription factor that binds CRE/AP-1 elements as homodimers or as heterodimers with Jun proteins (c-Jun, Jun-B, Jun-D), and operates predominantly as a chromatin-based epigenetic repressor whose activity is gated by stress-activated phosphorylation (PMID:8290251, PMID:26322480). In its basal unphosphorylated state, ATF7 occupies target promoters and recruits H3K9 methyltransferases — G9a and ESET — to deposit repressive H3K9me2/me3 marks and silence genes including Htr5b, UCP1, p16Ink4a, and subtelomeric TERRA loci (PMID:19893493, PMID:26322480, PMID:30826729, PMID:31294895). Upon stress or cytokine input (LPS, TNF-α, oxidative or dietary stress, high temperature), p38 MAPK phosphorylates conserved N-terminal threonines (Thr51/Thr53) in a sequential two-step mechanism, releasing ATF7 from chromatin, lowering repressive marks, and derepressing targets — a switch that underlies innate immunological memory in macrophages, stress-induced and intergenerational telomere shortening transmitted through sperm, cellular senescence, and adipocyte differentiation (PMID:18950637, PMID:26322480, PMID:29490055, PMID:30407559, PMID:32197065). This repressor-to-activator switch is conserved in C. elegans, where the ortholog ATF-7 represses PMK-1 p38 MAPK-regulated innate immunity genes basally and is converted to an activator of pathogen-induced genes upon direct PMK-1 phosphorylation (PMID:20369020, PMID:30789901). ATF7 activity is further tuned by SUMO modification — which delays nuclear entry and is mutually exclusive with Thr51/53 phosphorylation (PMID:17264123, PMID:18950637) — by interaction with TAF12/TFIID that potentiates activation (PMID:15735663), by CDK1/cyclin-B phosphorylation at Thr51/53 and Thr112 during mitosis that stabilizes ATF7 and supports G2/M progression and cyclin D1 expression (PMID:25545367, PMID:26101806), and by a cytoplasmic splice isoform (ATF7-4) that sequesters the activating kinase (PMID:21858082). Beyond repression, ATF7 directly activates target promoters such as PINK1 to support mitophagy and intestinal epithelial repair (PMID:31958521, PMID:40586859).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1994 High

    Established ATF7 as a bZIP dimerizing factor, defining its DNA-binding partners and a built-in negative regulatory architecture.

    Evidence Reciprocal Co-IP, EMSA and reporter assays showing ATFa/c-Jun heterodimers binding ATF/CRE/AP1 sites; a dominant-inhibitory splice form lacking the transactivation domain blocks full-length ATFa and binds NF-κB p50

    PMID:8288576 PMID:8290251

    Open questions at the time
    • Endogenous target genes not yet identified
    • Functional consequence of NF-κB p50 binding unresolved
  2. 1995 Medium

    Mapped the dimerization determinant and distinguished ATF7 functionally from its relative ATF2.

    Evidence GST pulldown with domain deletion localizing the leucine zipper requirement; reporter assays showing pRb differentially inhibits ATFa versus ATF2

    PMID:7702840 PMID:7786026

    Open questions at the time
    • pRb effect shown only in reporter context with no direct binding
    • In vivo relevance of pRb modulation unaddressed
  3. 1996 Medium

    Defined ATF7's nuclear localization and revealed a stable association with JNK2, framing the N-terminus as a regulatory hub.

    Evidence Chromosomal mapping, nuclear localization by transfection imaging, and Co-IP identifying associated 54/55 kDa JNK2 with domain-mapped binding sites

    PMID:8649858 PMID:8939888

    Open questions at the time
    • Whether JNK2 binding regulates ATF7 transcription directly unclear
    • NLS mapping not validated by mutagenesis
  4. 1999 Medium

    Showed the N-terminal Thr51/Thr53 region functions as a kinase-docking platform rather than a kinase substrate, identifying the residues central to ATF7 regulation.

    Evidence Site-directed mutagenesis of Thr51/Thr53, in vivo phosphorylation and reporter assays demonstrating JNK2 docking delivers kinase to ATF7 partners such as JunD

    PMID:10376527

    Open questions at the time
    • The kinase ultimately phosphorylating Thr51/53 not defined here
    • Physiological signals engaging docking unknown
  5. 2000 Medium

    Identified mAM as an ATF7-associated modulator linking ATF7 to the basal transcription machinery.

    Evidence Yeast two-hybrid, Co-IP, co-localization and ATPase/reporter assays showing mAM downregulates activity via TFIIE/TFIIH/Pol II contacts

    PMID:10777215

    Open questions at the time
    • Single lab; mechanism of repression not reconstituted
    • Endogenous role of mAM-ATF7 axis untested
  6. 2001 Medium

    Connected ATF7 to a phosphatase, indicating its activity is reversibly controlled by phosphorylation.

    Evidence Yeast two-hybrid, Co-IP and in vitro dephosphorylation mapping the PRL-1 interaction to the ATF7 bZIP region

    PMID:11278933

    Open questions at the time
    • Which ATF7 phospho-sites PRL-1 targets in vivo unknown
    • Cellular outcome of dephosphorylation not shown
  7. 2005 High

    Defined TAF12/TFIID as the coactivator bridging ATF7 to transcriptional activation.

    Evidence Reciprocal Co-IP, ChIP co-occupancy at an ATF7-responsive promoter, and reporter assays with TAF4 competition and isoform-specific domain mapping

    PMID:15735663

    Open questions at the time
    • Genome-wide TAF12-dependent ATF7 targets not mapped
    • Regulation of the TAF12-ATF7 interaction by signaling addressed only later
  8. 2007 High

    Established SUMO as a negative ATF7 modification that acts by blocking nuclear entry and TAF12 association.

    Evidence In vitro and in vivo sumoylation at an IKEE motif, localization tracking, TAF12 Co-IP, and promoter binding assays with site mutants

    PMID:17264123

    Open questions at the time
    • SUMO E3 specificity in physiological cells unclear
    • Desumoylation triggers not defined
  9. 2008 High

    Resolved the activating phosphorylation as a sequential two-step p38β2 cascade mutually exclusive with sumoylation, unifying the PTM logic of ATF7.

    Evidence In vitro kinase assays, phospho-mutants, Co-IP and reporter assays showing Thr53-then-Thr51 phosphorylation enhances TAF12 binding and excludes SUMO

    PMID:18950637

    Open questions at the time
    • Identity of the priming Thr53 kinase not established
    • Stress inputs upstream of p38β2 not all defined
  10. 2009 High

    First demonstrated ATF7 as a chromatin repressor in vivo, linking H3K9 methylation to a stress-responsive behavioral phenotype.

    Evidence ChIP at the Htr5b promoter, ATF7-ESET Co-IP, and Atf7 knockout mice showing derepressed Htr5b and abnormal behavior after social isolation

    PMID:19893493

    Open questions at the time
    • Generality of ESET versus G9a recruitment not yet resolved
    • Direct ESET recruitment mechanism unmapped
  11. 2010 High

    Showed the repressor-to-activator switch is evolutionarily conserved and central to innate immunity via genetic epistasis.

    Evidence C. elegans loss- and gain-of-function alleles and PMK-1/ATF-7 biochemistry placing ATF-7 downstream of p38 in immunity gene control

    PMID:20369020

    Open questions at the time
    • Genome-wide targets not yet defined (addressed in 2019)
    • Mammalian conservation of immunity role shown later
  12. 2011 Medium

    Identified a cytoplasmic splice isoform that gates ATF7 activation by kinase sequestration, adding a post-translational off-switch.

    Evidence Splicing characterization, fractionation, Co-IP, ubiquitination and reporter assays showing ATF7-4 sequesters the Thr53 kinase until stimulus-induced degradation

    PMID:21858082

    Open questions at the time
    • Identity of sequestered kinase not named
    • Tissue-specific abundance of ATF7-4 unknown
  13. 2013 Medium

    Extended the ATF7-TAF12 activation axis to vitamin-D-responsive gene control in osteoclast precursors.

    Evidence Reciprocal Co-IP, ChIP and siRNA knockdown showing ATF7 supports 1,25-(OH)2D3-induced CYP24A1 and TAF12 promoter binding

    PMID:23426901

    Open questions at the time
    • Direct ATF7 promoter occupancy at CYP24A1 not distinguished from TAF12-mediated
    • Single cell-type context
  14. 2014 Medium

    Revealed a stress-independent mitotic role: CDK1-cyclin B1 phosphorylation of ATF7 supports cell-cycle progression.

    Evidence In vitro kinase assay, phospho-mutants, siRNA knockdown and FACS showing mitotic Thr51/53 phosphorylation enables G2/M progression and Aurora activation

    PMID:25545367

    Open questions at the time
    • Mechanistic link between ATF7 and Aurora activation indirect
    • Transcriptional versus non-transcriptional contribution unclear
  15. 2015 High

    Established ATF7 as the molecular basis of innate immunological memory and clarified its mitotic stabilization.

    Evidence ChIP, G9a Co-IP, ATF7 KO and p38 inhibition showing LPS-driven release lowers H3K9me2 long-term; phospho-Thr112 intrabody and CRISPR studies link mitotic phosphorylation to ATF7 stability and cyclin D1

    PMID:26101806 PMID:26322480

    Open questions at the time
    • Duration and maintenance mechanism of the open chromatin state incompletely defined
    • Thr112 kinase recognition determinants unmapped
  16. 2018 High

    Defined ATF7 as a guardian of telomere integrity whose stress-induced release shortens telomeres.

    Evidence ChIP at telomeres, Ku-complex Co-IP, p38 inhibition and ATF7 KO mice showing TNF-α-driven release of ATF7 and telomerase causes telomere shortening

    PMID:29490055

    Open questions at the time
    • How ATF7 anchors telomerase mechanistically unresolved
    • Whether telomere effect requires H3K9 methylation here untested
  17. 2019 High

    Demonstrated ATF7 mediates intergenerational epigenetic inheritance and broadened its target landscape and physiological roles.

    Evidence ChIP/ChIP-seq, KO and conditional mice across germ cells (TERRA), adipose (UCP1), senescence (p16Ink4a), intestine, and genome-wide C. elegans occupancy, with sperm RNA and offspring phenotypes

    PMID:30407559 PMID:30789901 PMID:30826729 PMID:31294895 PMID:31958521

    Open questions at the time
    • Selectivity of ATF7 for specific loci across tissues not fully explained
    • Mechanism of transgenerational RNA transmission downstream of ATF7 incomplete
  18. 2020 High

    Showed dietary stress reprograms offspring metabolism through ROS-p38-ATF7 control of germline chromatin and sperm small RNAs.

    Evidence Genome-wide ChIP-seq in testicular germ cells, Atf7+/- genetics, low-protein-diet intervention, sperm small RNA profiling and offspring liver transcriptomics

    PMID:32197065

    Open questions at the time
    • Causal link between specific tRNA fragments and offspring phenotype incomplete
    • How LPD signals reach germ cell p38 not fully defined
  19. 2023 Medium

    Connected ATF7 to senescence/aging suppression and to a piRNA-controlled necroptosis axis, expanding its disease relevance.

    Evidence Overexpression/knockdown with H3K9me2 ChIP, NF-κB reporters and C. elegans lifespan; HNEAP-DNMT1-m5C control of Atf7 mRNA with ATF7 ChIP at the Chmp2a promoter and in vivo I/R injury

    PMID:37163432 PMID:37870216

    Open questions at the time
    • Direct ATF7 occupancy at SASP/NF-κB loci not fully mapped
    • Whether necroptosis role is repression-mediated as for other targets unclear
  20. 2024 Medium

    Identified an AP-1 context in leukemia where ATF7/JDP2 dimers recruit IRF2BP2 to restrain inflammatory gene activation.

    Evidence Co-IP of ATF7/JDP2/IRF2BP2, ChIP showing IRF2BP2 recruitment, and IRF2BP2 KO with transcriptomic and proliferation readouts in AML cells

    PMID:38801077

    Open questions at the time
    • Direct contribution of ATF7 versus JDP2 to dimer function not dissected
    • Phospho-regulation of this dimer untested
  21. 2025 Medium

    Demonstrated a direct gene-activating role for ATF7 driving mitophagy and intestinal protection via PINK1.

    Evidence ChIP-seq and luciferase assays at the PINK1 promoter with IEC-specific ATF7 KO showing impaired mitophagy and exacerbated DSS colitis

    PMID:40586859

    Open questions at the time
    • Whether PINK1 activation requires phosphorylated ATF7 not addressed
    • How ATF7 toggles between repression and activation at different loci unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural and signaling determinants that direct ATF7 to specific loci and dictate whether it acts as an H3K9-methylation repressor or a direct activator remain unresolved.
  • No structural model of chromatin-bound ATF7 or its methyltransferase-recruiting interface
  • Determinants of locus-specific repression versus activation undefined
  • Priming kinase for Thr53 unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0140110 transcription regulator activity 4 GO:0060090 molecular adaptor activity 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 2
Partners
EHMT2IRF2BP2JDP2JUNMAPK9PTP4A1SETDB1TAF12
Complex memberships
AP-1 (ATF7/Jun and ATF7/JDP2 dimers)TFIID

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 ATF7 (ATFa) proteins heterodimerize with c-Jun, Jun-B, and Jun-D (but not effectively with c-Fos for DNA binding), and ATFa/c-Jun heterodimers bind ATF, CRE, and AP1 sites; coexpression of c-Jun stimulates ATFa-dependent reporter activity. A C-terminal element negatively interferes with ATFa intrinsic activation. These interactions were confirmed by reciprocal co-immunoprecipitation and EMSA with in vitro synthesized proteins, and ATFa/c-Jun complexes were detected in HeLa cell extracts. Reciprocal co-immunoprecipitation, EMSA (electrophoretic band-shift assay), in vitro transcription/translation, transient transfection reporter assays Oncogene High 8290251
1994 ATF-a0, a splice variant of ATF7 (ATFa) lacking the P/S/T-rich transactivation domain, has no transactivating function on the E-selectin NF-ELAM1/deltaA element and acts as a dominant inhibitor when heterodimerized with full-length ATFa, completely blocking its transactivating activity. Both ATFa forms bind the p50 subunit of NF-κB as shown by affinity chromatography. Transient transfection reporter assays, RT-PCR, Northern blot, affinity chromatography The Journal of biological chemistry Medium 8288576
1995 ATFa interacts with c-Jun and c-Fos in vivo; complexes containing ATFa and either c-Jun or c-Fos were specifically retained on glutathione-agarose beads from crude extracts of transfected cells expressing GST-ATFa fusions. The leucine zipper domain of ATFa is essential for this interaction. GST pulldown from mammalian cell extracts, immunoblot, domain deletion analysis BioTechniques Medium 7702840
1995 The retinoblastoma gene product (pRb) differentially modulates ATFa and ATF2: co-expression of pRb strongly inhibits ATFa transcriptional activity on the TGF-β2 promoter CRE element, while it has additive or greater stimulatory effects with ATF2, revealing a functional distinction between these two related factors. Transient transfection reporter assays in CHO cells, in vitro DNA binding (CRE element) Archives of biochemistry and biophysics Low 7786026
1996 ATF7 (ATFa) is associated in vivo with JNK/SAP kinase activity (identified as 54/55 kDa JNK2) as revealed by co-immunoprecipitation from whole cell extracts. Two independent regions mediate kinase binding: the major site is within N-terminal residues 1–82 (containing the metal-chelating element); a weaker site is in the basic region preceding the leucine zipper. Co-immunoprecipitation from whole cell extracts, in vitro binding assays, in vivo kinase assays, immunological characterization Oncogene Medium 8649858
1996 The ATFa gene maps to chromosome 12 (band 12q13); ATFa isoforms are generated by alternative splice donor site usage; ATFa protein accumulates in the nucleus of transfected cells and the nuclear localization signal was mapped to the region adjacent to the leucine zipper domain. A minimal promoter of ~200 bp retains near-full transcriptional activity. Chromosomal mapping, expression analysis, nuclear localization by transfection/immunofluorescence, DNase I footprinting, Northern blot The Journal of biological chemistry Medium 8939888
1999 The N-terminal activation domain of ATF7 (ATFa) requires specific threonine residues (Thr51 and Thr53) in addition to the metal-binding domain for transcriptional activation. Although the N-terminal domain stably binds JNK2, ATFa is not itself a JNK2 substrate in vivo; instead, the N-terminal domain serves as a JNK2-docking site, allowing ATFa-associated partners such as JunD to be phosphorylated by the bound kinase. Site-directed mutagenesis of Thr51/Thr53, in vivo phosphorylation assays, transient transfection reporter assays, co-immunoprecipitation Oncogene Medium 10376527
2000 A novel protein mAM (mouse ATFa-associated Modulator, 1306 residues) was identified by yeast two-hybrid screening using the N-terminal half of ATF7 as bait. mAM colocalizes and interacts with ATFa in mammalian cells, contains a bipartite NLS, possesses ATPase activity, and downregulates transcriptional activity in an ATPase-independent manner by interacting with components of the basal transcription machinery (TFIIE, TFIIH, and RNA Pol II itself). Yeast two-hybrid, co-immunoprecipitation, co-localization, ATPase assay, transient transfection reporter assays Oncogene Medium 10777215
2001 ATF-7 physically interacts with the PRL-1 protein-tyrosine phosphatase; the interaction was initially identified by yeast two-hybrid and confirmed biochemically. The interaction maps to ATF-7's bZIP region and PRL-1's phosphatase domain. PRL-1 is able to dephosphorylate ATF-7 in vitro. ATF-7 homodimers bind CRE elements specifically. Yeast two-hybrid, co-immunoprecipitation, in vitro dephosphorylation assay, EMSA (CRE binding) The Journal of biological chemistry Medium 11278933
2005 ATF7 interacts directly with TAF12 (hsTAF12, a subunit of TFIID), and this interaction potentiates ATF7-induced transcriptional activation. Overexpression of hsTAF12 stimulates ATF7-dependent transcription; ChIP confirms ATF7-TAF12 co-occupancy at an ATF7-responsive promoter in vivo. TAF12-mediated activation is competitively inhibited by TAF4. Both TAF12 isoforms (TAF12-1 and -2) interact with the ATF7 activation region through their histone-fold domain, but only TAF12-1 mediates activation through its N-terminal region. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), transient transfection reporter assays, domain deletion analysis Oncogene High 15735663
2007 ATF7 is sumoylated in vitro (using RanBP2 as E3 SUMO ligase) and in vivo at a consensus IKEE motif within its N-terminal activation domain. Sumoylation delays ATF7 nuclear entry and inhibits its transcriptional activity by (i) impairing its association with TAF12 and (ii) blocking binding to specific sequences within target promoters. In vitro sumoylation assay, in vivo sumoylation (immunoprecipitation), nuclear localization tracking, co-immunoprecipitation, reporter assays, site-directed mutagenesis Nucleic acids research High 17264123
2008 p38β2 MAPK phosphorylates ATF7 at Thr51 in a sequential two-step mechanism: an unknown kinase first phosphorylates Thr53, which then permits p38β2 to phosphorylate Thr51. EGF treatment triggers this cascade. Phosphorylation at Thr51/53 and sumoylation of ATF7 are mutually exclusive modifications; phosphorylation increases ATF7 transcriptional activity via enhanced TAF12 association, while excluding sumoylation. In vitro kinase assays, site-directed mutagenesis (phospho-mimetic/phospho-deficient mutants), co-immunoprecipitation, reporter assays Journal of molecular biology High 18950637
2009 ATF7 silences transcription of the serotonin receptor 5B gene (Htr5b) by directly binding its 5'-regulatory region and mediating histone H3-K9 trimethylation via interaction with the ESET histone methyltransferase. Upon social isolation stress, ATF7 is phosphorylated via p38 and released from the Htr5b promoter, upregulating Htr5b. Atf7-deficient mice exhibit abnormal behavior and increased Htr5b mRNA in the dorsal raphe nucleus. ChIP, co-immunoprecipitation (ATF7-ESET interaction), Atf7 knockout mouse phenotype, quantitative RT-PCR The EMBO journal High 19893493
2010 C. elegans ATF-7, an ortholog of mammalian ATF2/ATF7, functions as a repressor of PMK-1 p38 MAPK-regulated innate immunity genes in the basal state and switches to an activator upon direct phosphorylation by PMK-1. Loss-of-function mutations in atf-7 restore basal expression of PMK-1-regulated genes in pmk-1 null mutants (genetic epistasis), but pathogen-induced gene induction by P. aeruginosa PA14 is abrogated in atf-7 loss-of-function animals. Genetic epistasis (loss-of-function and gain-of-function allele analysis), biochemical characterization of ATF-7/PMK-1 interaction, gene expression analysis PLoS genetics High 20369020
2011 A cytoplasmic alternatively spliced isoform of ATF7, named ATF7-4, inhibits both ATF7 and ATF2 transcriptional activity by blocking the first phosphorylation event on Thr53/Thr71 residues. ATF7-4 sequesters the Thr53-phosphorylating kinase in the cytoplasm. Upon stimulus-induced phosphorylation, ATF7-4 is poly-ubiquitinated and degraded, releasing the kinase and enabling ATF7/ATF2 activation. Alternative splicing characterization, co-immunoprecipitation, subcellular fractionation, phosphorylation assays (phospho-specific antibodies), ubiquitination assays, reporter assays PloS one Medium 21858082
2013 ATF7 physically interacts with TAF12 in osteoclast (OCL) precursors (confirmed by reciprocal co-immunoprecipitation). ATF7 contributes to 1,25-(OH)2D3-induced CYP24A1 (24-hydroxylase) gene expression; knockdown of ATF7 in MVNP-expressing OCL precursors decreases CYP24A1 induction by 1,25-(OH)2D3 and reduces TAF12 binding to the CYP24A1 promoter (by ChIP). Reciprocal co-immunoprecipitation, chromatin immunoprecipitation (ChIP), siRNA knockdown, reporter/gene expression assays Journal of bone and mineral research Medium 23426901
2014 Cdk1-cyclin B1 phosphorylates ATF7 at Thr51/Thr53 from early prophase to anaphase during mitosis (in the absence of stress). Knockdown of ATF7 decreases cell proliferation rate and M-phase cell number. Expression of a mitotically non-phosphorylatable ATF7 mutant inhibits G2/M progression despite endogenous ATF7 presence. Mitotic phosphorylation of ATF7 promotes activation of Aurora kinases. In vitro kinase assay (Cdk1-cyclin B1), phospho-specific antibodies, siRNA knockdown, cell cycle analysis (FACS), phospho-deficient/phospho-mimetic mutant expression PloS one Medium 25545367
2015 ATF7 mediates innate immunological memory in macrophages by suppressing innate immunity genes through recruitment of the histone H3K9 dimethyltransferase G9a to chromatin. LPS treatment induces p38-mediated phosphorylation of ATF7, causing its release from chromatin and a decrease in repressive H3K9me2 marks; the partially open chromatin structure and increased basal expression of target genes are maintained long-term. ChIP (ATF7 chromatin binding and H3K9me2 levels), co-immunoprecipitation (ATF7-G9a interaction), ATF7 knockout/knockdown, p38 inhibitor treatment, LPS stimulation experiments Nature immunology High 26322480
2015 ATF7 phosphorylation on residue Thr112 occurs exclusively during mitosis and is CDK1/cyclin B-dependent. ATF7 is excluded from condensed chromatin during mitosis. Thr112 phosphorylation protects ATF7 from proteasomal degradation (demonstrated using a transduced neutralizing intrabody), but does not affect displacement from condensed chromatin. ATF7 silencing by CRISPR/Cas9 decreases cyclin D1 protein levels, suggesting ATF7 re-localizes to chromatin after telophase to drive cyclin D1 expression. Phospho-specific antibodies, CDK1 inhibitor treatment, transduced neutralizing monoclonal antibody (intrabody), phospho-mimetic/phospho-deficient mutants, CRISPR/Cas9 knockdown, immunofluorescence Cell cycle Medium 26101806
2018 ATF7 and telomerase are localized on telomeres via interactions with the Ku complex. In response to TNF-α, ATF7 is phosphorylated by p38, leading to the release of ATF7 and telomerase from telomeres and resulting in telomere shortening. ATF7-deficient mice show telomere shortening consistent with this mechanism. ChIP (ATF7 and telomerase at telomeres), co-immunoprecipitation (ATF7-Ku complex), p38 inhibitor treatment, ATF7 KO mouse model, telomere length measurement Nucleic acids research High 29490055
2019 TNF-α induces p38-dependent phosphorylation of ATF7 in mouse testicular germ cells, causing release of ATF7 from the TERRA gene promoter in the subtelomeric region, disrupting heterochromatin and inducing TERRA (telomere repeat-containing RNA). This TERRA is transgenerationally transmitted to zygotes via sperm and causes telomere shortening in offspring. ChIP (ATF7 at TERRA promoter, H3K9me2 levels), p38 inhibitor treatment, ATF7 KO mouse model, TERRA measurement, sperm RNA analysis Nucleic acids research High 30407559
2019 In C. elegans, PMK-1-ATF-7 signaling regulates a majority of all genes induced by P. aeruginosa infection. ATF-7 occupies regulatory regions of pathogen-induced genes in a PMK-1-dependent manner (ChIP-Seq). A subset of ATF-7-regulated pathogen-induced target genes directly contribute to host defense. RNA-seq, ChIP-Seq (ATF-7 genome-wide occupancy), functional analysis of target gene knockdowns PLoS genetics High 30789901
2019 ATF7 is required for adipocyte differentiation; it interacts with histone dimethyltransferase G9a in adipocytes to repress interferon-stimulated genes (which suppress adipogenesis). ATF7 binds transcriptional regulatory regions of the UCP1 gene and silences it by controlling H3K9 dimethylation. Ablation of ATF7 promotes beige fat biogenesis in inguinal white adipose tissue. ATF7 KO mouse model, ChIP (ATF7 at UCP1 promoter, H3K9me2 levels), co-immunoprecipitation (ATF7-G9a), differentiation assays iScience Medium 30826729
2019 ATF7 binds the p16Ink4a gene promoter and recruits H3K9 di- and trimethyltransferases to silence p16Ink4a expression. With age or oxidative stress, p38-mediated phosphorylation of ATF7 increases and ATF7 is released from the promoter, leading to decreased H3K9me2 at the locus and accelerated p16Ink4a accumulation. Atf7-/- mice have shorter lifespans than wild-type mice. ChIP (ATF7 occupancy and H3K9me2 at p16Ink4a promoter), ATF7 KO mice (lifespan and p16 mRNA quantification), MEF culture with oxidative stress, p38 phosphorylation assays Genes to cells Medium 31294895
2020 ATF7 binds the promoter regions of ~2,300 genes including cholesterol biosynthesis-related and tRNA genes in testicular germ cells (TGCs). A paternal low-protein diet (LPD) induces ROS, which activates p38 to phosphorylate ATF7 in TGCs; this leads to ATF7 release from chromatin, decreased H3K9me2 on target genes, and increased tRNA fragment expression in spermatozoa. These epigenetic changes are transmitted to offspring and alter liver gene expression and metabolism. Atf7+/- mutation phenocopies paternal LPD effects. ChIP-seq (ATF7 genome-wide binding in TGCs, H3K9me2 levels), Atf7+/- mouse genetics, dietary intervention (LPD), ROS measurement, spermatozoa small RNA profiling, offspring liver transcriptomics Molecular cell High 32197065
2020 ATF2 and ATF7 are required for intestinal epithelial repair but dispensable for homeostasis. Activating phosphorylation of ATF2 and ATF7 occurs mainly in intestinal crypts. Intestine-specific double-mutant mice show impaired regenerative response to DSS or irradiation, with increased apoptosis, severe ulceration, and failure to regenerate colonic crypts. Organoids from double-mutant epithelium show growth disadvantage and impaired wound healing. Conditional KO mouse model (Villin-CreERT2), DSS colitis model, irradiation model, organoid culture, phospho-specific antibodies (IHC), scratch assay Cellular and molecular gastroenterology and hepatology Medium 31958521
2022 ATF7 accumulates in the nucleus of porcine embryos and localizes to pericentromeric heterochromatin after the late 4-cell stage, co-localizing with HP1. ATF7 knockdown reduces blastocyst rate and cell number, and decreases HP1 and H3K9me2 levels. High temperature induces p38 phosphorylation of ATF7, reducing H3K9me2 and HP1 levels; inhibition of p38 activity alleviates these effects. siRNA knockdown, immunofluorescence (ATF7 localization, HP1, H3K9me2), p38 inhibitor treatment, blastocyst rate and cell count Cell proliferation Medium 36254813
2023 ATF7 inhibits NF-κB signaling and increases H3K9 dimethylation (H3K9me2) to suppress cellular senescence and SASP secretion. Loss of ATF7 induces cellular senescence while overexpression delays it. In C. elegans, ATF7 overexpression suppresses aging biomarkers and extends lifespan. ATF7 overexpression and knockdown, H3K9me2 ChIP, NF-κB reporter assays, senescence assays (SA-β-gal, p21 levels), C. elegans lifespan assay Aging and disease Medium 37163432
2023 HNEAP (a piRNA) interacts with DNMT1 and reduces m5C methylation of Atf7 mRNA, increasing ATF7 protein levels. Elevated ATF7 then downregulates transcription of Chmp2a (an inhibitor of necroptosis), reducing CHMP2A levels and promoting cardiomyocyte necroptosis. Loss of HNEAP inhibits necroptosis and improves cardiac function in I/R-injured mice. RNA pulldown (HNEAP-DNMT1 interaction), m5C methylation assay, ATF7 ChIP (binding to Chmp2a promoter), luciferase reporter assay, ATF7 knockdown/overexpression, HNEAP KO mouse model Advanced science Medium 37870216
2024 ATF7 forms an AP-1 heterodimer with JDP2 in AML cells; IRF2BP2 is recruited by the ATF7/JDP2 dimer to chromatin and counteracts its gene-activating function on inflammatory pathway genes. Loss of IRF2BP2 leads to overactivation of inflammatory pathways and strongly reduced cell proliferation. Co-immunoprecipitation (ATF7/JDP2/IRF2BP2 complex), ChIP (IRF2BP2 recruitment by ATF7/JDP2), IRF2BP2 knockdown/KO with transcriptomic and proliferation readouts Nucleic acids research Medium 38801077
2025 ATF7 directly binds to and transcriptionally activates the PINK1 promoter (a master mitophagy regulator) as demonstrated by ChIP-seq and luciferase reporter assays. Loss of ATF7 or PINK1 in intestinal epithelial cells impairs mitophagy, disrupts mitochondrial membrane potential, increases ROS, and exacerbates DSS-induced colitis in vivo. ChIP-seq, luciferase reporter assay, IEC-specific ATF7 KO mouse model, mitophagy assays (electron microscopy, mitochondrial membrane potential), DSS colitis model FASEB journal Medium 40586859

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Phosphorylation of the conserved transcription factor ATF-7 by PMK-1 p38 MAPK regulates innate immunity in Caenorhabditis elegans. PLoS genetics 152 20369020
2015 The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory. Nature immunology 146 26322480
2011 Aspergillus nidulans transcription factor AtfA interacts with the MAPK SakA to regulate general stress responses, development and spore functions. Molecular microbiology 129 21320182
2010 AtfA bZIP-type transcription factor regulates oxidative and osmotic stress responses in Aspergillus nidulans. Molecular genetics and genomics : MGG 86 20131067
2014 The role of AtfA and HOG MAPK pathway in stress tolerance in conidia of Aspergillus fumigatus. Fungal genetics and biology : FG & B 81 25459537
1994 Jun and Fos heterodimerize with ATFa, a member of the ATF/CREB family and modulate its transcriptional activity. Oncogene 76 8290251
2001 ATF-7, a novel bZIP protein, interacts with the PRL-1 protein-tyrosine phosphatase. The Journal of biological chemistry 68 11278933
2018 miRNA-103a-3p Promotes Human Gastric Cancer Cell Proliferation by Targeting and Suppressing ATF7 in vitro. Molecules and cells 67 29754469
2020 ATF7-Dependent Epigenetic Changes Are Required for the Intergenerational Effect of a Paternal Low-Protein Diet. Molecular cell 65 32197065
2016 Comparative transcriptome analysis revealing dormant conidia and germination associated genes in Aspergillus species: an essential role for AtfA in conidial dormancy. BMC genomics 60 27185182
2009 Aspergillus oryzae atfA controls conidial germination and stress tolerance. Fungal genetics and biology : FG & B 59 19770065
1995 Eukaryotic GST fusion vector for the study of protein-protein associations in vivo: application to interaction of ATFa with Jun and Fos. BioTechniques 55 7702840
2019 Global transcriptional regulation of innate immunity by ATF-7 in C. elegans. PLoS genetics 52 30789901
2009 Social isolation stress induces ATF-7 phosphorylation and impairs silencing of the 5-HT 5B receptor gene. The EMBO journal 49 19893493
2023 HNEAP Regulates Necroptosis of Cardiomyocytes by Suppressing the m5 C Methylation of Atf7 mRNA. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 35 37870216
2018 ATF7 mediates TNF-α-induced telomere shortening. Nucleic acids research 32 29490055
2019 Telomere shortening by transgenerational transmission of TNF-α-induced TERRA via ATF7. Nucleic acids research 31 30407559
1999 Role of the ATFa/JNK2 complex in Jun activation. Oncogene 29 10376527
2000 A murine ATFa-associated factor with transcriptional repressing activity. Oncogene 28 10777215
1994 ATF-a0, a novel variant of the ATF/CREB transcription factor family, forms a dominant transcription inhibitor in ATF-a heterodimers. The Journal of biological chemistry 27 8288576
2007 Sumoylation delays the ATF7 transcription factor subcellular localization and inhibits its transcriptional activity. Nucleic acids research 26 17264123
2005 A functional interaction between ATF7 and TAF12 that is modulated by TAF4. Oncogene 26 15735663
1996 Structure and expression of the ATFa gene. The Journal of biological chemistry 25 8939888
1996 In vivo association of ATFa with JNK/SAP kinase activities. Oncogene 23 8649858
2017 Transcriptome-Based Modeling Reveals that Oxidative Stress Induces Modulation of the AtfA-Dependent Signaling Networks in Aspergillus nidulans. International journal of genomics 22 28770220
2014 Production of triacylglycerols in Escherichia coli by deletion of the diacylglycerol kinase gene and heterologous overexpression of atfA from Acinetobacter baylyi ADP1. Applied microbiology and biotechnology 22 24389701
2014 Functional analysis of atfA gene to stress response in pathogenic thermal dimorphic fungus Penicillium marneffei. PloS one 22 25365258
2020 Quantitative and Qualitative Analyses of Triacylglycerol Production in the Wild-Type Cyanobacterium Synechocystis sp. PCC 6803 and the Strain Expressing AtfA from Acinetobacter baylyi ADP1. Plant & cell physiology 20 32433767
2023 Longevity-Associated Transcription Factor ATF7 Promotes Healthspan by Suppressing Cellular Senescence and Systematic Inflammation. Aging and disease 19 37163432
2020 ATF2 and ATF7 Are Critical Mediators of Intestinal Epithelial Repair. Cellular and molecular gastroenterology and hepatology 19 31958521
2021 Genetic Interactions Between Aspergillus fumigatus Basic Leucine Zipper (bZIP) Transcription Factors AtfA, AtfB, AtfC, and AtfD. Frontiers in fungal biology 18 37744135
2014 Cdk1-mediated phosphorylation of human ATF7 at Thr-51 and Thr-53 promotes cell-cycle progression into M phase. PloS one 18 25545367
2008 p38beta2-mediated phosphorylation and sumoylation of ATF7 are mutually exclusive. Journal of molecular biology 17 18950637
2011 A cytoplasmic negative regulator isoform of ATF7 impairs ATF7 and ATF2 phosphorylation and transcriptional activity. PloS one 15 21858082
2019 The Transcription Factor ATF7 Controls Adipocyte Differentiation and Thermogenic Gene Programming. iScience 14 30826729
2022 Functional analysis of the bZIP-type transcription factors AtfA and AtfB in Aspergillus nidulans. Frontiers in microbiology 13 36204617
2021 AtfA-Independent Adaptation to the Toxic Heavy Metal Cadmium in Aspergillus nidulans. Microorganisms 12 34361869
2017 Identification of ATF-7 and the insulin signaling pathway in the regulation of metallothionein in C. elegans suggests roles in aging and reactive oxygen species. PloS one 12 28632756
2021 Loss of muscleblind splicing factor shortens Caenorhabditis elegans lifespan by reducing the activity of p38 MAPK/PMK-1 and transcription factors ATF-7 and Nrf/SKN-1. Genetics 11 34849877
2020 miR-340-5p inhibits sheep adipocyte differentiation by targeting ATF7. Animal science journal = Nihon chikusan Gakkaiho 10 33190272
2013 Role of ATF7-TAF12 interactions in the vitamin D response hypersensitivity of osteoclast precursors in Paget's disease. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 10 23426901
2022 ATF7-dependent epigenetic changes induced by high temperature during early porcine embryonic development. Cell proliferation 9 36254813
2024 IRF2BP2 counteracts the ATF7/JDP2 AP-1 heterodimer to prevent inflammatory overactivation in acute myeloid leukemia (AML) cells. Nucleic acids research 6 38801077
2019 Stress-induced and ATF7-dependent epigenetic change influences cellular senescence. Genes to cells : devoted to molecular & cellular mechanisms 6 31294895
1995 Interaction of retinoblastoma gene product with transcription factors ATFa and ATF2. Archives of biochemistry and biophysics 6 7786026
2015 ATF7 is stabilized during mitosis in a CDK1-dependent manner and contributes to cyclin D1 expression. Cell cycle (Georgetown, Tex.) 5 26101806
2014 AtfA, a new factor in global regulation of transcription in Acinetobacter spp. Molecular microbiology 5 25047957
2005 Characterization and expression pattern of two zebrafish atf7 genes. Developmental dynamics : an official publication of the American Association of Anatomists 5 15906372
2024 ChIP-Seq Analysis of AtfA Interactions in Aspergillus flavus Reveals Its Involvement in Aflatoxin Metabolism and Virulence Under Oxidative Stress. International journal of molecular sciences 4 39596279
2025 ATF7-PINK1 Axis Governs Mitophagy and Intestinal Inflammation in Ulcerative Colitis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 3 40586859
2025 CircSARS-CV2-N1368 from SARS-CoV-2 impairs endothelial cell function through the upregulation of ATF7 to activate TLR4/NF-κB/ROS signaling. Acta pharmacologica Sinica 2 40069492
2025 Epigenomic Profiling Positions ATF7 as a Core Regulator of Colonic Inflammation. Journal of cellular and molecular medicine 0 40903840
2025 Genome-Wide Mapping Reveals an Extensive AtfA Regulatory Influence on Development, Metabolism, and Stress Preparedness in Aspergillus nidulans. Cells 0 41439985

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