Affinage

DACH1

Dachshund homolog 1 · UniProt Q9UI36

Length
758 aa
Mass
78.6 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DACH1 is a transcriptional corepressor and chromatin-associated cofactor that integrates TGF-β/BMP, AP-1, estrogen receptor, NF-κB, and Wnt signaling to regulate cell proliferation, differentiation, epithelial-mesenchymal transition, and organ morphogenesis. DACH1 directly binds DNA at Forkhead-like sequences and is recruited to target promoters through interactions with c-Jun, Smad4, ERα, SNAI1, p53, p65, and HOXA9, where its conserved DS domain recruits corepressor complexes containing NCoR, HDAC1/2, and Sin3a to silence genes including cyclin D1, FGF2, MMP9, Bim, and ATF6 (PMID:14525983, PMID:17182846, PMID:20351289, PMID:19605405, PMID:34772908, PMID:36754276). DACH1 operates within the Six-Eya-Dach retinal determination network, where Eya phosphatase activity switches the Six1-Dach complex from repression to activation via CBP recruitment, and this network is essential for Müllerian duct development, limb patterning, coronary artery formation, and kidney tubule homeostasis (PMID:14628042, PMID:12215533, PMID:18395837, PMID:28779009, PMID:33998598). DACH1 protein stability is regulated by HDAC4-mediated SUMOylation and proteasomal degradation, while its interaction with PTIP modulates promoter H3K4Me3 levels; additionally, an intronic lncRNA (LncDACH1) independently regulates SERCA2a stability and SRSF1/β-catenin signaling in cardiac and pulmonary contexts (PMID:27239042, PMID:33998601, PMID:31446800, PMID:36176913).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2002 High

    The molecular basis of how DACH1 participates in Six-Eya-Dach transcriptional complexes was unknown; demonstration that Dach binds chromatin DNA via its DD1 domain and connects to Eya indirectly through CBP established DACH1 as a chromatin-associated cofactor requiring CBP for transcriptional synergy with Six-Eya.

    Evidence Mammalian two-hybrid, GST pulldown, chromatin immunoprecipitation on reconstituted chromatin templates, reporter assays in cultured cells

    PMID:12215533

    Open questions at the time
    • Whether DACH1 DD1 domain binds specific DNA sequences was unresolved
    • Structural basis of CBP-mediated Dach-Eya bridging undefined
    • In vivo relevance of CBP requirement not tested
  2. 2003 High

    How DACH1 interfaces with TGF-β signaling was unknown; identification of direct Smad4 binding and DS-domain-dependent NCoR recruitment established DACH1 as a corepressor that antagonizes Smad-mediated transcription, with Eya phosphatase subsequently shown to switch the Six1-Dach complex from repression to activation.

    Evidence Endogenous Co-IP of Smad4 and NCoR, Smad4-null cell rescue, reporter assays, microarray (PMID:14525983); Eya phosphatase enzymatic assays and Six1 knockout mouse epistasis (PMID:14628042)

    PMID:14525983 PMID:14628042

    Open questions at the time
    • How Eya phosphatase biochemically displaces corepressors from the Dach complex was not defined
    • Direct phosphatase substrate on DACH1 not identified
  3. 2004 High

    Whether DACH1-Smad repression extended to BMP signaling and had developmental consequences was untested; demonstration that Dach1 binds Sin3a and the Smad complex to repress BMP transcription in chick limb established DACH1 as a repressor of both TGF-β and BMP pathways with roles in limb patterning.

    Evidence Co-IP/pulldown of Smad and Sin3a complexes, in vivo chick limb AER manipulations, reporter assays

    PMID:15280207

    Open questions at the time
    • Whether Sin3a and NCoR act redundantly or in distinct DACH1 complexes was unclear
    • How DACH1 selects between TGF-β and BMP target genes was not addressed
  4. 2006 High

    Whether DACH1 directly represses cell cycle genes and functions as a tumor suppressor was unknown; discovery that DACH1 binds c-Jun and recruits HDAC1/2/NCoR to repress cyclin D1 and AP-1 targets, inhibiting breast cancer cell proliferation and tumor growth, defined its tumor-suppressive mechanism.

    Evidence ChIP at cyclin D1 promoter, cyclin D1 KO epistasis, Co-IP of c-Jun/HDAC1/2/NCoR, Cre-mediated c-jun excision rescue, in vivo xenograft models

    PMID:16980615 PMID:17182846

    Open questions at the time
    • Whether DACH1-c-Jun repression operates in normal tissues versus only cancer cells was unclear
    • Relative contribution of HDAC1 vs HDAC2 not dissected
  5. 2008 High

    The in vivo requirement of Dach1 in reproductive tract development was undefined; Dach1/Dach2 double knockout mice revealed redundant roles in Müllerian duct formation through regulation of Lim1 and Wnt7a expression.

    Evidence Double knockout mice with histological and in situ hybridization analysis

    PMID:18395837

    Open questions at the time
    • Whether DACH1 directly binds Lim1/Wnt7a promoters was not tested
    • Individual contribution of Dach1 vs Dach2 in MD development remained unclear
  6. 2009 High

    Whether DACH1 intersects with estrogen receptor signaling was unknown; identification of direct DS-domain-mediated ERα binding and PELP1 as a DACH1-interacting coactivator revealed that DACH1 restrains ERα transcriptional activity at endogenous ER response elements.

    Evidence Reciprocal Co-IP, ChIP at endogenous ERE, proteomic identification of PELP1, domain mutagenesis

    PMID:19605405

    Open questions at the time
    • How estradiol displaces DACH1 corepressors to allow PELP1-dependent activation was not fully resolved
    • Whether DACH1-ERα interaction occurs in normal mammary tissue was not tested
  7. 2010 High

    Whether DACH1 binds DNA sequence-specifically genome-wide was unresolved; ChIP-seq and CAST identified DACH1 binding to FOX-like DNA motifs and showed it antagonizes FOXM1 promoter occupancy, establishing DACH1 as a sequence-specific DNA-binding transcriptional repressor at Forkhead target gene clusters.

    Evidence CAST in vitro selection, ChIP-seq, genome-wide promoter analysis, chromatin-context reporter assays

    PMID:20351289

    Open questions at the time
    • Crystal structure of DACH1-DNA complex not determined
    • Whether DACH1-FOXM1 competition is direct or involves chromatin remodeling intermediaries was unclear
  8. 2011 High

    Whether DACH1 regulates cancer stem cell properties was unknown; demonstration that DACH1 directly binds the FGF2 promoter to repress bFGF transcription, suppressing glioma tumor-initiating cell activity that could be rescued by exogenous bFGF, linked DACH1 to stem cell signaling.

    Evidence ChIP at FGF2 promoter, doxycycline-inducible DACH1 expression, in vivo tumor transplantation with bFGF rescue

    PMID:21750150

    Open questions at the time
    • Whether DACH1 represses FGF2 in normal neural progenitors was not tested
    • Corepressor complex identity at FGF2 promoter not determined
  9. 2015 High

    How DACH1 suppresses EMT mechanistically was incompletely defined; identification of direct DACH1-SNAI1 complex formation at the E-cadherin E-box, converting SNAI1 from a repressor to permitting E-cadherin activation, provided a specific anti-EMT mechanism distinct from its AP-1-based repression.

    Evidence Reciprocal Co-IP, ChIP at E-cadherin promoter, EMT marker analysis, in vivo metastasis model

    PMID:25775416

    Open questions at the time
    • Whether DACH1 displaces SNAI1 corepressors or blocks their recruitment was not resolved
    • Specificity for SNAI1 over SNAI2 was shown but the structural basis was undefined
  10. 2016 High

    How DACH1 protein stability is regulated was unknown; discovery that HDAC4 promotes DACH1 SUMOylation and proteasomal degradation, and that in obesity CaMKII-mediated HDAC4 cytoplasmic sequestration stabilizes DACH1 to repress ATF6 and disrupt hepatic insulin signaling, revealed a post-translational regulatory circuit for DACH1 abundance.

    Evidence In vivo mouse obesity models, liver-targeted shRNA for HDAC4 and DACH1, Co-IP, SUMOylation/ubiquitination assays, ATF6 reporter assays

    PMID:27239042

    Open questions at the time
    • The E3 SUMO ligase mediating DACH1 SUMOylation was not identified
    • Whether HDAC4 directly catalyzes SUMOylation or acts indirectly was unclear
  11. 2017 High

    Whether DACH1 functions in vascular endothelial biology was untested; endothelial-specific Dach1 deletion demonstrated that DACH1 drives endothelial polarization and migration against flow via CXCL12/CXCR4 signaling, and is required for proper coronary artery growth.

    Evidence Endothelial-specific Dach1 KO mice, CXCL12/CXCR4 pharmacological inhibition, shear stress culture experiments, coronary artery morphometry

    PMID:28779009

    Open questions at the time
    • Whether DACH1 directly binds the CXCL12 promoter was not shown by ChIP
    • How shear stress regulates DACH1 expression at the molecular level was not defined
  12. 2018 Medium

    Whether DACH1 directly engages p53 was unknown; Co-IP showed DACH1 binds p53 directly and upregulates p53 levels to suppress HCC proliferation, while SIX1 opposes p53 only indirectly through DACH1, integrating DACH1 into p53 tumor-suppressive signaling.

    Evidence Co-IP with Flag-DACH1 and His-SIX1, immunofluorescence co-localization, in vivo xenograft

    PMID:29333942

    Open questions at the time
    • Whether DACH1 stabilizes p53 protein or upregulates p53 transcription was not distinguished
    • Tagged overexpression system lacks endogenous validation
    • Mechanism of SIX1-mediated p53 downregulation through DACH1 was not elucidated
  13. 2019 High

    Whether the DACH1 intronic lncRNA (LncDACH1) has independent function was unknown; demonstration that LncDACH1 directly binds SERCA2a and promotes its ubiquitination-dependent degradation, impairing cardiac calcium handling, established LncDACH1 as a functionally distinct product of the DACH1 locus.

    Evidence RNA pulldown/direct binding assay, ubiquitination assay, cardiac-specific LncDACH1 transgenic OE and conditional KO mice, calcium transient measurements

    PMID:31446800

    Open questions at the time
    • The E3 ubiquitin ligase recruited by LncDACH1 to SERCA2a was not identified
    • Whether LncDACH1 expression is coordinately regulated with DACH1 mRNA was not addressed
  14. 2021 High

    How DACH1 regulates chromatin state at target promoters was mechanistically incomplete; identification of DACH1-PTIP interaction showed that DACH1 is recruited to promoters where it reduces H3K4Me3 marks, and podocyte/tubule-specific knockout models demonstrated that loss of DACH1 derepresses target genes causing kidney fibrosis and diabetic kidney injury.

    Evidence Co-IP of DACH1-PTIP, ChIP for H3K4Me3, single-cell RNA-seq, podocyte-specific and tubule-specific Dach1 KO and OE mice, CRISPR validation of risk variants

    PMID:33998598 PMID:33998601

    Open questions at the time
    • Whether DACH1 displaces PTIP from the MLL complex or sequesters it was not resolved
    • Complete catalog of DACH1-repressed kidney genes was not established
    • Whether DACH1 H3K4Me3 reduction is the primary mechanism at all target loci is unknown
  15. 2021 High

    Whether DACH1 regulates NF-κB-dependent invasion genes was untested; demonstration that DACH1 binds p65 and c-Jun at the MMP9 promoter NF-κB/AP-1 sites and recruits HDAC1 to deacetylate p65, repressing MMP9 transcription and breast cancer invasion, unified DACH1's AP-1 and NF-κB corepressor functions at a single target gene.

    Evidence Co-IP of DACH1 with p65 and c-Jun, ChIP at MMP9 promoter, HDAC1 recruitment and p65 acetylation assays, invasion assays

    PMID:34772908

    Open questions at the time
    • Whether DACH1-mediated p65 deacetylation affects other NF-κB target genes beyond MMP9 was not tested
    • Relative importance of AP-1 vs NF-κB sites in MMP9 repression was not dissected
  16. 2022 High

    Whether LncDACH1 functions beyond the heart was unknown; discovery that LncDACH1 directly binds SRSF1 to suppress β-catenin accumulation, protecting against pulmonary fibrosis, broadened LncDACH1's roles to a second organ system and splicing-related regulatory mechanism.

    Evidence RNA-protein pulldown, LncDACH1 KO mice with spontaneous pulmonary fibrosis, SRSF1 OE rescue, BLM fibrosis model

    PMID:36176913

    Open questions at the time
    • Specific RNA splicing events altered by LncDACH1-SRSF1 interaction were not cataloged
    • Whether LncDACH1 affects SRSF1 in cardiac tissue was not tested
  17. 2024 High

    Whether DACH1 participates in ferroptosis regulation was unknown; demonstration that DACH1 promotes p53 Ser392 phosphorylation and mitochondrial translocation, where p53 binds SLC25A37 to drive mitochondrial iron overload and ferroptosis in hepatic stellate cells, identified DACH1 as a ferroptosis modulator stabilized by ferroptosis inducers.

    Evidence CRISPR KO, Co-IP/pulldown of DACH1-p53 and p53-SLC25A37, Ser392 mutagenesis, mitochondrial fractionation, in vivo hepatic fibrosis model

    PMID:38437058

    Open questions at the time
    • The kinase mediating p53 Ser392 phosphorylation downstream of DACH1 was not identified
    • Whether DACH1-driven ferroptosis occurs in cell types beyond hepatic stellate cells is untested
    • The ubiquitin ligase whose activity is suppressed by ferroptosis inducers to stabilize DACH1 was not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of DACH1 DNA binding and DS-domain corepressor recruitment, how DACH1 selects among its many promoter targets in different cell types, the identity of E3 ligases controlling DACH1 ubiquitination and the SUMO ligase for SUMOylation, and whether DACH1 protein and LncDACH1 functionally interact or are regulated coordinately.
  • No crystal or cryo-EM structure of DACH1 or its complexes exists
  • Context-dependent target gene selection mechanism is undefined
  • Coordination between DACH1 protein and LncDACH1 functions is unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 13 GO:0098772 molecular function regulator activity 4 GO:0003677 DNA binding 2 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 6 GO:0005929 cilium 1
Pathway
R-HSA-74160 Gene expression (Transcription) 12 R-HSA-1643685 Disease 6 R-HSA-1266738 Developmental Biology 4 R-HSA-1640170 Cell Cycle 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-4839726 Chromatin organization 1
Partners
ESR1EYA1JUNNCOR1PTIPSMAD4SNAI1TP53
Complex memberships
NCoR/HDAC1/HDAC2 corepressor complexSin3a corepressor complexSix1-Eya-Dach retinal determination complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 DACH1 inhibits TGF-β signaling by binding to Smad4 and NCoR in cultured cells; the DACH1 DS domain is required and sufficient for NCoR binding at a Smad4-binding site, and Smad4 is required for DACH1 repression of Smad signaling. Co-immunoprecipitation of endogenous Smad4 and NCoR, co-localization in nuclear dot-like structures, gene reporter assays, microarray analyses, and Smad4-null cell rescue experiments The Journal of biological chemistry High 14525983
2002 Dach interacts with Eya indirectly through CBP (CREB-binding protein) to mediate transcriptional synergy; the Dach DD1 domain binds chromatin DNA directly, and synergistic activation with Six-Eya requires CBP recruitment. Mammalian two-hybrid, GST pulldown, chromatin immunoprecipitation with reconstituted chromatin DNA template, reporter assays, E1A CBP-binding mutant experiments Molecular and cellular biology High 12215533
2003 Eya phosphatase activity switches the Six1-Dach complex from transcriptional repression to activation, and this switch requires Eya enzymatic function to recruit co-activators to specific gene targets regulating precursor cell proliferation. Phosphatase activity assays, genetic interaction studies (Six1 knockout mice), gene reporter assays, co-activator recruitment experiments Nature High 14628042
2006 DACH1 represses cyclin D1 transcription through a c-Jun DNA-binding partner, requiring the DACH1 DS alpha-helical domain which recruits corepressors to local chromatin, thereby inhibiting breast cancer cell DNA synthesis and tumor growth. Genetic deletion studies (cyclin D1 knockout), reporter assays, chromatin immunoprecipitation, in vivo xenograft tumor models, loss-of-function and gain-of-function cell experiments Molecular and cellular biology High 16980615
2006 DACH1 binds c-Jun and inhibits AP-1 transcriptional activity; it coprecipitates HDAC1, HDAC2, and NCoR, repressing c-Jun target genes (cyclin A, β-PAK, stathmin) through the c-Jun delta domain, requiring the DS domain of DACH1. Co-immunoprecipitation, reporter assays with c-jun deletion mutants, Cre-mediated c-jun excision rescue experiment, transcriptional repression assays Molecular biology of the cell High 17182846
2009 DACH1 binds ERα (estrogen receptor-α) via its DS domain to inhibit ERα transcriptional activity; DACH1 associates with ERα at endogenous ER response elements, and proteomic analysis identified PELP1 as a DACH1-binding partner (requiring the DACH1 C-terminus) that serves as an ERα coactivator when E2 disengages DACH1 corepressors. Co-immunoprecipitation/Western blotting, chromatin immunoprecipitation, proteomic analysis, domain mutagenesis, DNA synthesis and proliferation assays Cancer research High 19605405
2010 DACH1 binds a DNA sequence resembling the FOX (Forkhead) binding site; genome-wide ChIP-seq mapped DACH1 binding to FOX target gene clusters, and DACH1 antagonized FOXM1 target gene expression and promoter occupancy in the context of local chromatin. CAST (cyclic amplification and selection of targets), ChIP coupled with high-throughput sequencing (ChIP-seq), genome-wide in silico promoter analysis, chromatin-context reporter assays Proceedings of the National Academy of Sciences of the United States of America High 20351289
2013 DACH1 suppresses EMT by repressing YB-1-mediated oncogenic transcription in the nucleus and by inactivating YB-1-dependent cytoplasmic translational induction of Snail, thereby blocking both transcriptional and translational control of cell invasion. KD/OE in breast cancer cell lines with functional invasion assays, in vivo mammary tumor models, molecular pathway analysis connecting DACH1 to nuclear and cytoplasmic YB-1 functions Cancer research Medium 24335958
2015 DACH1 directly interacts with SNAI1 (but not SNAI2) to form a complex that binds the E-box on the E-cadherin promoter in a SNAI1-dependent manner, inhibiting SNAI1 transcriptional activity and activating E-cadherin expression to suppress EMT and breast cancer metastasis. Co-immunoprecipitation, ChIP at E-cadherin promoter, overexpression/knockdown in breast cancer cell lines with EMT marker analysis, in vivo mouse metastasis model Oncogenesis High 25775416
2004 Chick Dach1 interacts with the Smad complex and the corepressor Sin3a to repress BMP-mediated transcription, controlling apical ectodermal ridge (AER) formation and proximodistal patterning in limb development. Co-immunoprecipitation/pulldown of Smad complex and Sin3a, in vivo chick limb manipulations, reporter assays for BMP-mediated transcription Development (Cambridge, England) High 15280207
2016 In obesity, CaMKII phosphorylates HDAC4, preventing its nuclear translocation; nuclear HDAC4 normally SUMOylates DACH1, targeting it for proteasomal degradation. Loss of HDAC4 nuclear activity stabilizes DACH1, which together with NCoR represses Atf6 transcription, activating a PERK-TRB3 pathway that disrupts hepatic insulin signaling. In vivo mouse obesity models, liver-targeted shRNA knockdown of HDAC4 and DACH1, co-immunoprecipitation, ubiquitination/SUMOylation assays, ATF6 promoter reporter assays Cell reports High 27239042
2018 DACH1 represses ATF6/PLAT (tPA gene) transcription in hepatocytes via an NCoR corepressor complex; hepatocyte-DACH1 knockout mice show increased liver Plat, circulating tPA, and fibrinolytic activity, whereas ATF6 knockout shows opposite effects, establishing an ATF6-tPA pathway repressed by DACH1. Hepatocyte-specific DACH1 knockout and ATF6 knockout mice, hepatocyte Plat silencing, promoter reporter assays, fibrinolysis functional assays Blood High 30504459
2011 DACH1 transcriptionally represses FGF2/bFGF, reducing tumor-initiating (cancer stem) cell activity in glioma; ChIP confirmed direct DACH1 binding to the FGF2 promoter, and exogenous bFGF rescued spheroid formation and tumorigenicity suppressed by DACH1. Chromatin immunoprecipitation, doxycycline-inducible DACH1 expression, gene expression analysis, in vivo subcutaneous tumor transplantation, rescue with exogenous bFGF Proceedings of the National Academy of Sciences of the United States of America High 21750150
2017 DACH1 stimulates endothelial cell polarization and migration against flow by activating CXCL12 expression; DACH1 is regulated by shear stress quality (maintained by low/variable flow, downregulated by high laminar flow), and CXCL12/CXCR4 inhibition reverses DACH1-driven migration. Endothelial-specific Dach1 deletion results in small coronary arteries and reduced endothelial cell polarization. Endothelial-specific Dach1 knockout mice, CXCL12/CXCR4 pharmacological inhibition, shear stress culture experiments, overexpression and functional migration assays, in vivo coronary artery morphometry Genes & development High 28779009
2021 DACH1 binds PTIP (an essential component of the H3K4Me3 activating complex) and is recruited to promoter-binding sites, repressing transcription by reducing promoter H3K4Me3 levels; DACH1 knockdown combined with hyperglycemia triggers target gene upregulation and increased H3K4Me3. Co-immunoprecipitation (DACH1-PTIP interaction), ChIP for H3K4Me3, single-cell RNA sequencing, in silico promoter analysis, podocyte-specific Dach1 KO and overexpression mouse models The Journal of clinical investigation High 33998601
2021 Tubule-specific Dach1 deletion leads to more severe renal fibrosis (in folic acid and diabetic injury models), while tubule-specific overexpression is protective; ChIP and single-cell RNA-seq indicate DACH1 controls cell cycle and myeloid chemotactic factor expression contributing to macrophage infiltration. CRISPR-Cas9 editing confirmed risk variants regulate DACH1 expression. Tubule-specific Dach1 KO and overexpression mouse models, CRISPR-Cas9 gene editing, ChIP, single-cell RNA-seq, TWAS/Mendelian randomization for genetic association The Journal of clinical investigation High 33998598
2012 In myeloid progenitor cells, forced DACH1 expression increases cyclin D1, D3, Cdk 4/6, and p27Kip1 while repressing p21Cip1; DACH1 knockdown decreases cyclins D1/D3/F and Cdks, increases p21Cip1, and reduces Rb phosphorylation, blocking cell cycle progression. Forced expression and shRNA knockdown in HL-60 myeloid cells, cell cycle analysis by flow cytometry, Western blot for cyclins and CDKs Biochemical and biophysical research communications Medium 22405764
2012 DACH1 forms an endogenous complex with HOXA9 mediated by the DACH1 C-terminus in t(9;11) leukemia cells, promoting myeloid progenitor colonogenic activity; C/EBPα and GATA-1 bind the DACH1 promoter as transcriptional suppressors. Co-immunoprecipitation of endogenous HOXA9-DACH1 complex, ChIP for C/EBPα and GATA-1 at DACH1 promoter, ectopic expression experiments Biochemical and biophysical research communications Medium 22902925
2018 DACH1 and SIX1 co-localize and DACH1 immunoprecipitates both p53 and SIX1; DACH1 overexpression up-regulates p53 to suppress HCC proliferation while SIX1 overexpression down-regulates p53. DACH1 can pull down p53 directly, while SIX1 interacts with p53 only indirectly through DACH1. Immunofluorescence co-localization, co-immunoprecipitation with Flag-DACH1 and His-SIX1, in vivo xenograft model, Western blot Cancer biology & therapy Medium 29333942
2021 DACH1 inhibits breast cancer cell invasion by repressing MMP9 transcription; DACH1 interacts with p65 and c-Jun at the NF-κB and AP-1 binding sites in the MMP9 promoter, and the DACH1-p65 association recruits HDAC1 to reduce p65 acetylation and transcriptional activity. Co-immunoprecipitation of DACH1 with p65 and c-Jun, ChIP at MMP9 promoter NF-κB/AP-1 sites, HDAC1 recruitment assay, p65 acetylation analysis, invasion assays Cell death discovery High 34772908
2015 DACH1 represses cyclin D1 transcription through association with AP-1 protein in renal cancer cells, inhibiting S-phase progression and tumor growth. Co-immunoprecipitation, reporter gene assays, Western blot, in vivo xenograft assays Journal of hematology & oncology Medium 25322986
2019 LncRNA-DACH1 (an intronic lncRNA of DACH1) directly binds SERCA2a protein and promotes its ubiquitination-related degradation, thereby impairing cardiac calcium handling and cardiac function; cardiac-specific knockout of LncDACH1 increases SERCA2a expression and improves cardiac function. RNA pulldown/direct binding assay, ubiquitination assay, transgenic overexpression and conditional knockout mouse models, calcium transient measurements, adenoviral KD/OE Hypertension (Dallas, Tex. : 1979) High 31446800
2022 LncRNA DACH1 (lncDACH1) directly binds SRSF1 protein, decreasing its activity and inhibiting accumulation of Ctnnb1 (β-catenin), thereby protecting against pulmonary fibrosis; LncDACH1 KO mice develop spontaneous pulmonary fibrosis, and SRSF1 overexpression blocks the anti-fibrotic effect of LncDACH1. RNA-protein pulldown/binding assays, lncDACH1 knockout mice, overexpression in BLM fibrosis model, siRNA rescue of SRSF1, Western blot for Ctnnb1, functional fibrosis assays Acta pharmaceutica Sinica. B High 36176913
2024 DACH1 modulates ferroptosis by inducing phosphorylation of p53 at serine 392, promoting mitochondrial translocation of p53; mitochondrial p53 binds SLC25A37 to enhance mitochondrial iron uptake causing iron overload and ferroptosis. DACH1 protein is stabilized by ferroptosis inducers via suppression of the ubiquitin-proteasome pathway. CRISPR-Cas9 DACH1 knockout, co-immunoprecipitation/pulldown of DACH1-p53 and p53-SLC25A37, p53 phospho-serine 392 mutagenesis, mitochondrial fractionation, in vivo hepatic fibrosis mouse model with HSC-specific knockdowns Hepatology communications High 38437058
2023 DACH1 inhibits S100A8 expression in breast cancer cells; stable DACH1 overexpression significantly decreases S100A8 generation in vitro and in xenograft tumor models. Stable DACH1 overexpression in breast cancer cells, ELISA for S100A8 secretion, in vivo xenograft tumor assays with Western blot Biomarker research Medium 38093319
2002 BOR syndrome mutations S486P and L504R in EYA1 impair Dach1 protein-protein interactions as demonstrated by mammalian two-hybrid and GST-pulldown assays, with conformational changes detected by altered protease sensitivity. Mammalian two-hybrid assay, GST-pulldown assay, limited proteolysis (trypsin/V8 protease sensitivity) Journal of human genetics Medium 11950062
2008 Dach1 and Dach2 are redundantly required for Müllerian duct (female reproductive tract) development; in Dach1/2 double mutants, MD expression of Lim1 and Wnt7a is abnormal and MD development is disrupted, while Wolffian duct development is unaffected. Dach1/Dach2 double knockout mice, histological analysis, in situ hybridization for Lim1 and Wnt7a expression Genesis (New York, N.Y. : 2000) High 18395837
2018 In the adrenal zona glomerulosa, DACH1 suppresses aldosterone secretion by activating TGF-β signaling; DACH1 silencing in H295R cells increases CYP11B2 mRNA and aldosterone production, while overexpression decreases aldosterone and activates TGF-β and canonical Wnt but inhibits noncanonical Wnt signaling. DACH1 siRNA knockdown and overexpression in H295R adrenocortical cells, CYP11B2 mRNA measurement, aldosterone ELISA, Wnt and TGF-β pathway reporter assays Hypertension (Dallas, Tex. : 1979) Medium 25776071
2002 Mouse Dach1 is expressed in the developing retina, brain, and limbs; sequence analysis identifies two conserved motifs (DD1 and DD2) in the protein, with DD1 sharing similarity to the N-terminal Ski/SnoN sequences involved in transformation and differentiation. cDNA cloning, sequence analysis, in situ hybridization, FISH chromosomal localization Development genes and evolution Medium 10502109
2020 In colorectal cancer, DACH1 functions as a tumor promoter by suppressing BMP signaling via SMAD4; DACH1 co-immunoprecipitates with SMAD4, and DACH1 overexpression stimulates colonsphere and tumor organoid formation in the context of dysregulated BMP signaling. Co-immunoprecipitation of DACH1-SMAD4, CRISPR/Cas9 deletion, lentiviral OE and shRNA KD, intestinal organoid models, xenotransplants, microarray data analysis EBioMedicine High 32512510
2023 Dach1 in type II alveolar epithelial cells represses Bim expression by forming a complex with c-Jun that binds the Bim promoter, thereby inhibiting alveolar epithelial apoptosis and protecting against pulmonary fibrosis. Co-immunoprecipitation/pulldown of Dach1-c-Jun complex, ChIP at Bim promoter, lung-specific Dach1 overexpression in BLM mice, siRNA knockdown in primary AECII cells, apoptosis assays Translational research : the journal of laboratory and clinical medicine High 36754276
2021 siRNA-mediated depletion of DACH1 reveals a key role in ciliogenesis and cilia function; DACH1 protein localizes to the base of primary cilia as shown by advanced microscopy. siRNA-mediated DACH1 depletion, advanced microscopy imaging for DACH1 localization at primary cilia base, homology modeling of missense variant Genomics Medium 34022343
2018 Metformin induces DACH1 expression through AMPK phosphorylation, and DACH1 in turn inhibits NF-κB activity to reduce CXCL1 secretion, thereby blocking MDSC migration; knockdown of AMPK or DACH1 abrogates metformin's effect on MDSC chemotaxis. siRNA knockdown of AMPK and DACH1, CXCL1 secretion measurement, MDSC migration assays, in vivo xenograft with adoptive MDSC transfer, flow cytometry Oncoimmunology Medium 29900050

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature 534 14628042
2003 DACH-LIGA homocystein (german, austrian and swiss homocysteine society): consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. Clinical chemistry and laboratory medicine 192 14656016
2007 Pax-Six-Eya-Dach network during amphioxus development: conservation in vitro but context specificity in vivo. Developmental biology 136 17477914
2003 DACH1 inhibits transforming growth factor-beta signaling through binding Smad4. The Journal of biological chemistry 125 14525983
2002 Molecular interaction and synergistic activation of a promoter by Six, Eya, and Dach proteins mediated through CREB binding protein. Molecular and cellular biology 122 12215533
2006 DACH1 is a cell fate determination factor that inhibits cyclin D1 and breast tumor growth. Molecular and cellular biology 107 16980615
1999 Mouse Dach, a homologue of Drosophila dachshund, is expressed in the developing retina, brain and limbs. Development genes and evolution 92 10502109
2018 Metformin blocks myeloid-derived suppressor cell accumulation through AMPK-DACH1-CXCL1 axis. Oncoimmunology 86 29900050
2017 DACH1 stimulates shear stress-guided endothelial cell migration and coronary artery growth through the CXCL12-CXCR4 signaling axis. Genes & development 80 28779009
2013 Epigenetic regulation of DACH1, a novel Wnt signaling component in colorectal cancer. Epigenetics 78 24149323
2001 Dach1 mutant mice bear no gross abnormalities in eye, limb, and brain development and exhibit postnatal lethality. Molecular and cellular biology 78 11238885
2015 DACH1 inhibits SNAI1-mediated epithelial-mesenchymal transition and represses breast carcinoma metastasis. Oncogenesis 75 25775416
2015 The DACH/EYA/SIX gene network and its role in tumor initiation and progression. International journal of cancer 74 26096807
2013 Cell fate factor DACH1 represses YB-1-mediated oncogenic transcription and translation. Cancer research 69 24335958
2006 Cell fate determination factor DACH1 inhibits c-Jun-induced contact-independent growth. Molecular biology of the cell 65 17182846
2021 Transcriptome-wide association analysis identifies DACH1 as a kidney disease risk gene that contributes to fibrosis. The Journal of clinical investigation 62 33998598
2013 Epigenetic silencing of DACH1 induces loss of transforming growth factor-β1 antiproliferative response in human hepatocellular carcinoma. Hepatology (Baltimore, Md.) 58 23787902
2012 Revisiting [PtCl₂(cis-1,4-DACH)]: an underestimated antitumor drug with potential application to the treatment of oxaliplatin-refractory colorectal cancer. Journal of medicinal chemistry 57 22788918
2009 The cell fate determination factor DACH1 is expressed in estrogen receptor-alpha-positive breast cancer and represses estrogen receptor-alpha signaling. Cancer research 57 19605405
2010 Attenuation of Forkhead signaling by the retinal determination factor DACH1. Proceedings of the National Academy of Sciences of the United States of America 55 20351289
2014 DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells. Journal of hematology & oncology 52 25322986
2005 Pax6-dependence of Six3, Eya1 and Dach1 expression during lens and nasal placode induction. Gene expression patterns : GEP 51 16024294
2002 Dach1, a vertebrate homologue of Drosophila dachshund, is expressed in the developing eye and ear of both chick and mouse and is regulated independently of Pax and Eya genes. Mechanisms of development 51 11804780
2002 Forebrain-specific promoter/enhancer D6 derived from the mouse Dach1 gene controls expression in neural stem cells. Neuroscience 50 12088753
2019 Long Noncoding RNA-DACH1 (Dachshund Homolog 1) Regulates Cardiac Function by Inhibiting SERCA2a (Sarcoplasmic Reticulum Calcium ATPase 2a). Hypertension (Dallas, Tex. : 1979) 47 31446800
2014 The negative regulators of Wnt pathway-DACH1, DKK1, and WIF1 are methylated in oral and oropharyngeal cancer and WIF1 methylation predicts shorter survival. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 46 25487617
2017 MicroRNA-552 promotes tumor cell proliferation and migration by directly targeting DACH1 via the Wnt/β-catenin signaling pathway in colorectal cancer. Oncology letters 45 28927149
2009 Altered expression of DACH1 and cyclin D1 in endometrial cancer. Cancer biology & therapy 45 19502783
2022 LncRNA DACH1 protects against pulmonary fibrosis by binding to SRSF1 to suppress CTNNB1 accumulation. Acta pharmaceutica Sinica. B 44 36176913
2016 Hepatocyte DACH1 Is Increased in Obesity via Nuclear Exclusion of HDAC4 and Promotes Hepatic Insulin Resistance. Cell reports 43 27239042
2002 Impaired interactions between mouse Eyal harboring mutations found in patients with branchio-oto-renal syndrome and Six, Dach, and G proteins. Journal of human genetics 43 11950062
2015 DACH1 inhibits lung adenocarcinoma invasion and tumor growth by repressing CXCL5 signaling. Oncotarget 40 25788272
2021 Dach1 Extends Artery Networks and Protects Against Cardiac Injury. Circulation research 37 34383559
2017 BMP6 Regulates Proliferation and Apoptosis of Human Sertoli Cells Via Smad2/3 and Cyclin D1 Pathway and DACH1 and TFAP2A Activation. Scientific reports 37 28387750
2015 MiR-217 Promotes Tumor Proliferation in Breast Cancer via Targeting DACH1. Journal of Cancer 37 25653720
2011 Homozygously deleted gene DACH1 regulates tumor-initiating activity of glioma cells. Proceedings of the National Academy of Sciences of the United States of America 37 21750150
2021 DACH1 protects podocytes from experimental diabetic injury and modulates PTIP-H3K4Me3 activity. The Journal of clinical investigation 36 33998601
2008 Conformer distribution in (cis-1,4-DACH)bis(guanosine-5'-phosphate)platinum(II) adducts: a reliable model for DNA adducts of antitumoral cisplatin. Inorganic chemistry 36 18284193
2014 Epigenetic silencing of DACH1 induces the invasion and metastasis of gastric cancer by activating TGF-β signalling. Journal of cellular and molecular medicine 34 24912879
2019 Cyclometalated Gold(III) Complexes Bearing DACH Ligands. Inorganic chemistry 33 31247820
2017 PtI2(DACH), the iodido analogue of oxaliplatin as a candidate for colorectal cancer treatment: chemical and biological features. Dalton transactions (Cambridge, England : 2003) 33 28229139
2017 DACH1 suppresses breast cancer as a negative regulator of CD44. Scientific reports 33 28659634
2004 Chick Dach1 interacts with the Smad complex and Sin3a to control AER formation and limb development along the proximodistal axis. Development (Cambridge, England) 33 15280207
2018 SIX1 and DACH1 influence the proliferation and apoptosis of hepatocellular carcinoma through regulating p53. Cancer biology & therapy 32 29333942
2008 Mouse Dach1 and Dach2 are redundantly required for Müllerian duct development. Genesis (New York, N.Y. : 2000) 32 18395837
2001 DACH: genomic characterization, evaluation as a candidate for postaxial polydactyly type A2, and developmental expression pattern of the mouse homologue. Genomics 32 11543628
2014 Synthesis, crystal structure and antiproliferative activity of Cu(II) nalidixic acid-DACH conjugate: comparative in vitro DNA/RNA binding profile, cleavage activity and molecular docking studies. European journal of medicinal chemistry 31 24826817
2010 A mechanistic approach for the DNA binding of chiral enantiomeric L- and D-tryptophan-derived metal complexes of 1,2-DACH: cleavage and antitumor activity. Chirality 31 20928895
2003 Tamoxifen derivatives for delivery of the antitumoral (DACH)Pt group: selective synthesis by McMurry coupling, and biochemical behaviour. Chembiochem : a European journal of chemical biology 31 12898627
2019 Regulation of cancer stem cell properties by SIX1, a member of the PAX-SIX-EYA-DACH network. Advances in cancer research 30 30691681
2014 Silencing DACH1 promotes esophageal cancer growth by inhibiting TGF-β signaling. PloS one 30 24743895
2018 An ATF6-tPA pathway in hepatocytes contributes to systemic fibrinolysis and is repressed by DACH1. Blood 29 30504459
2014 Synthesis and characterization of new transition metal {Cu(II), Ni(II) and Co(II)} L-phenylalanine-DACH conjugate complexes: in vitro DNA binding, cleavage and molecular docking studies. Journal of photochemistry and photobiology. B, Biology 29 24815057
1997 [Oxaliplatin: the first DACH platinum in clinical practice]. Bulletin du cancer 29 9295871
2012 DACH1 regulates cell cycle progression of myeloid cells through the control of cyclin D, Cdk 4/6 and p21Cip1. Biochemical and biophysical research communications 28 22405764
2002 Fibroblast growth factor signaling regulates Dach1 expression during skeletal development. Developmental dynamics : an official publication of the American Association of Anatomists 28 12203718
2020 Organoid modelling identifies that DACH1 functions as a tumour promoter in colorectal cancer by modulating BMP signalling. EBioMedicine 27 32512510
2015 Suppression of DACH1 promotes migration and invasion of colorectal cancer via activating TGF-β-mediated epithelial-mesenchymal transition. Biochemical and biophysical research communications 27 25778865
2018 The transcription factor Dach1 is essential for podocyte function. Journal of cellular and molecular medicine 26 29498212
2020 A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics. Nature immunology 24 33077975
2014 Evolution of the Pax-Six-Eya-Dach network: the calcisponge case study. EvoDevo 24 25002963
2012 Double homozygous missense mutations in DACH1 and BMP4 in a patient with bilateral cystic renal dysplasia. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 24 23262432
2021 DACH1 inhibits breast cancer cell invasion and metastasis by down-regulating the transcription of matrix metalloproteinase 9. Cell death discovery 23 34772908
2015 DACH1, a zona glomerulosa selective gene in the human adrenal, activates transforming growth factor-β signaling and suppresses aldosterone secretion. Hypertension (Dallas, Tex. : 1979) 23 25776071
2003 Targeted disruption of mouse Dach1 results in postnatal lethality. Developmental dynamics : an official publication of the American Association of Anatomists 23 12508235
2021 Biallelic variant in DACH1, encoding Dachshund Homolog 1, defines a novel candidate locus for recessive postaxial polydactyly type A. Genomics 22 34022343
2019 Long non-coding RNA HOTAIR regulates the development of non-small cell lung cancer through miR-217/DACH1 signaling pathway. European review for medical and pharmacological sciences 22 30720199
2016 Decreased DACH1 expression in glomerulopathy is associated with disease progression and severity. Oncotarget 22 27888806
2019 Dynamic and Cell-Specific DACH1 Expression in Human Neocortical and Striatal Development. Cerebral cortex (New York, N.Y. : 1991) 20 29688344
2017 Expression of genes and proteins of the pax-six-eya-dach network in the metamorphic sea urchin: Insights into development of the enigmatic echinoderm body plan and sensory structures. Developmental dynamics : an official publication of the American Association of Anatomists 20 28850769
2019 DACH1 suppresses epithelial to mesenchymal transition (EMT) through Notch1 pathway and reverses progestin resistance in endometrial carcinoma. Cancer medicine 19 31215145
2018 Neurotoxic effect of oxaliplatin: Comparison with its oxalate-free analogue cis-[PtII(1R,2R-DACH)(3-acetoxy-1,1-cyclobutanedicarboxylato)] (LLC-1402) in mice. Toxicology and applied pharmacology 19 29307816
2003 Synthesis, characterization and preliminary cytotoxicity assays of poly(ethylene glycol)-malonato-Pt-DACH conjugates. European journal of medicinal chemistry 18 12932905
2014 Familial young-onset diabetes, pre-diabetes and cardiovascular disease are associated with genetic variants of DACH1 in Chinese. PloS one 17 24465431
2012 Regulation of HOXA9 activity by predominant expression of DACH1 against C/EBPα and GATA-1 in myeloid leukemia with MLL-AF9. Biochemical and biophysical research communications 17 22902925
2020 DACH1, a novel target of miR-218, participates in the regulation of cell viability, apoptosis, inflammatory response, and epithelial-mesenchymal transition process in renal tubule cells treated by high-glucose. Renal failure 16 32408786
2019 Role of Dach1 revealed using a novel inner ear-specific Dach1-knockdown mouse model. Biology open 16 31405829
2016 DACH1 inhibits the proliferation and invasion of lung adenocarcinoma through the downregulation of peroxiredoxin 3. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 16 26810067
2023 S100A8/A9 as a risk factor for breast cancer negatively regulated by DACH1. Biomarker research 14 38093319
2020 DACH1 mutation frequency in endometrial cancer is associated with high tumor mutation burden. PloS one 14 33378353
2019 Evaluation of cytotoxic potential of structurally well-characterized RNA targeted ionic non-steroidal anti-inflammatory (NSAID) Cu(ii) & Zn(ii) DACH-mefenamato drug conjugates against human cancer cell lines. RSC advances 14 35492558
2020 The PAX-SIX-EYA-DACH network modulates GATA-FOG function in fly hematopoiesis and human erythropoiesis. Development (Cambridge, England) 13 31806659
2023 Dach1 deficiency drives alveolar epithelium apoptosis in pulmonary fibrosis via modulating C-Jun/Bim activity. Translational research : the journal of laboratory and clinical medicine 11 36754276
2016 Polymer nanoparticle delivery of dichloroacetate and DACH-Pt to enhance antitumor efficacy and lower systemic toxicity. Biomaterials science 11 26810463
2022 The optimal use of chlormethine gel for mycosis fungoides: An expert consensus from Germany, Austria and Switzerland (DACH region). Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG 10 35429108
2024 The cell fate regulator DACH1 modulates ferroptosis through affecting P53/SLC25A37 signaling in fibrotic disease. Hepatology communications 9 38437058
2016 Inhibition of DACH1 activity by short hairpin RNA represses cell proliferation and tumor invasion in pancreatic cancer. Oncology reports 9 27278537
2011 The type 1 insulin-like growth factor receptor and resistance to DACH1. Cell cycle (Georgetown, Tex.) 9 21558809
2021 Role of DACH1 on Proliferation, Invasion, and Apoptosis in Human Lung Adenocarcinoma Cells. Current molecular medicine 8 33463463
2021 New anticancer Pd and Pt complexes of tertamyl dithiocarbamate and DACH ligands against HT29 and Panc1 cell lines. Journal of biomolecular structure & dynamics 8 33645454
2018 Alteration of DACH1 methylation patterns in lung cancer contributes to cell proliferation and migration. Biochemistry and cell biology = Biochimie et biologie cellulaire 8 29590536
2018 DACH1 inhibits glioma invasion and tumor growth via the Wnt/catenin pathway. OncoTargets and therapy 8 30271168
2018 MicroRNA-6807-3p promotes the tumorigenesis of glioma by targeting downstream DACH1. Brain research 8 30527681
2016 Synthesis and crystal structure elucidation of new copper(II)-based chemotherapeutic agent coupled with 1,2-DACH and orthovanillin: Validated by in vitro DNA/HSA binding profile and pBR322 cleavage pathway. Journal of photochemistry and photobiology. B, Biology 8 27289445
2013 Focal cerebral ischemia induces the neurogenic potential of mouse Dach1-expressing cells in the dorsal part of the lateral ventricles. Neuroscience 8 23458709
2023 Study of DACH1 Expression and its Epigenetic Regulators as Possible Breast Cancer-Related Biomarkers. Avicenna journal of medical biotechnology 7 37034893
2022 The Function of circRNA-0047604 in Regulating the Tumor Suppressor Gene DACH1 in Breast Cancer. BioMed research international 7 35097124
2020 MiR-645 regulates the proliferation and apoptosis of diffuse large B-cell lymphoma by targeting DACH1. Human cell 7 32529465
2018 Effect of DACH1 on proliferation and invasion of laryngeal squamous cell carcinoma. Head & face medicine 7 30261897
1996 Efficacy of the platinum analog [Pt(cis-dach)(DPPE)-2NO3] on histocultured human patient bladder tumors and cancer cell lines. Anticancer research 7 9042201