Affinage

Showing DACH1 — DACH is a alias.

DACH1

Dachshund homolog 1 · UniProt Q9UI36

Length
758 aa
Mass
78.6 kDa
Annotated
2026-06-09
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DACH1 is a chromatin-associated transcriptional corepressor that constrains proliferation and cell-fate transitions across development, cancer, and tissue injury by docking onto pathway-specific effectors and delivering corepressor machinery to target promoters (PMID:16980615, PMID:20351289, PMID:33998598). It binds DNA through its conserved DD1 domain and occupies FOX-like sequence elements genome-wide (PMID:12215533, PMID:20351289), while its conserved DS domain recruits the NCoR–HDAC1/2 and Sin3a corepressors to local chromatin (PMID:14525983, PMID:17182846, PMID:15280207). Through this architecture DACH1 represses a broad set of effectors by direct physical association: it binds Smad4 to block TGF-β/Smad and AP-1 signaling (PMID:14525983), engages c-Jun to repress cyclin D1 and AP-1 targets (PMID:16980615, PMID:17182846), co-occupies estrogen-response elements with ERα (PMID:19605405), antagonizes FOXM1 occupancy (PMID:20351289), complexes with SNAI1 at the E-cadherin E-box to suppress EMT (PMID:25775416), and represses MMP9 by tethering HDAC1 to p65/c-Jun at NF-κB/AP-1 sites to reduce p65 acetylation (PMID:34772908). In kidney tubule and podocyte cells DACH1 recruits the PTIP–H3K4Me3 complex to its bound promoters and lowers promoter H3K4Me3, repressing chemotactic and cell-cycle genes and protecting against fibrosis and diabetic injury (PMID:33998598, PMID:33998601). DACH1 activity is integrated into the Six1–Eya–DACH network, where Eya phosphatase activity switches DACH1-containing complexes between repression and activation during organogenesis (PMID:12215533, PMID:14628042, PMID:11950062). Its abundance is set post-translationally: HDAC4-mediated SUMOylation targets DACH1 for proteasomal degradation, and stabilized DACH1 co-represses ATF6 with NCOR to control hepatocyte insulin signaling and tPA/fibrinolysis (PMID:27239042, PMID:30504459). DACH1 also acts through p53, inducing p53 Ser392 phosphorylation and mitochondrial translocation to drive SLC25A37-dependent ferroptosis (PMID:38437058). Beyond transcription, DACH1 localizes to the base of primary cilia and is required for ciliogenesis (PMID:34022343), and Dach1/Dach2 are redundantly required for Müllerian duct development (PMID:18395837).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2002 High

    Establishing how DACH1 contacts chromatin and cooperates within the Six-Eya-Dach module defined its biochemical mode of action as a context-switchable cofactor rather than an autonomous activator.

    Evidence GST pulldown, GAL4-reporter and chromatin-binding/CBP-recruitment assays mapping DNA binding to the DD1 domain; mammalian two-hybrid and GST pulldown defining direct Eya1-Dach1 interaction via disease mutations

    PMID:11950062 PMID:12215533

    Open questions at the time
    • Does not resolve sequence specificity of DD1 DNA contacts
    • Eya1-Dach1 interaction tested with tagged/in vitro proteins, not endogenous complexes
  2. 2002 Medium

    Placing Dach1 downstream of FGF and antagonized by BMP positioned it as an integrator of growth-factor signaling in skeletal patterning.

    Evidence FGF/BMP4 bead implantation in mouse limb bud organ culture with AER removal and rescue

    PMID:12203718

    Open questions at the time
    • Correlative expression changes without defined transcriptional mechanism
    • Does not establish direct regulators of the Dach1 locus
  3. 2003 High

    Identifying NCoR and Smad4 as DS-domain partners explained how DACH1 represses TGF-β/Smad and AP-1 signaling through corepressor recruitment.

    Evidence Endogenous reciprocal Co-IP, immunofluorescence co-localization, reporter assays, microarray of TGF-β targets, Smad4-null rescue

    PMID:14525983

    Open questions at the time
    • Does not define DACH1 promoter occupancy genome-wide
    • Stoichiometry of the DACH1-NCoR-Smad4 complex unresolved
  4. 2003 High

    Demonstrating that Eya phosphatase activity flips Six1-DACH complexes between repression and activation established the regulatory switch governing DACH1 output during organogenesis.

    Evidence Mouse genetic epistasis (Six1/Eya mutants), Eya phosphatase enzymatic assays, reporter assays, Co-IP

    PMID:14628042

    Open questions at the time
    • Direct phosphorylation substrate driving the switch not pinpointed
    • Whether DACH1 itself is dephosphorylated is not shown
  5. 2004 High

    Showing Dach1-Smad-Sin3a complexes repress BMP transcription extended the corepressor model into limb proximodistal patterning.

    Evidence Co-IP, in vivo chick limb gain/loss-of-function, reporter assays

    PMID:15280207

    Open questions at the time
    • Mapped in chick ortholog
    • Direct DNA contacts at BMP target promoters not defined
  6. 2006 High

    Linking DACH1 to cyclin D1 repression via c-Jun and corepressor recruitment connected its molecular activity to growth suppression and tumor inhibition.

    Evidence ChIP, reporter assays, cyclin D1 and c-jun genetic rescue/excision, xenograft tumor growth, domain mutagenesis

    PMID:16980615 PMID:17182846

    Open questions at the time
    • Whether DACH1 binds the cyclin D1 promoter directly or only via c-Jun not fully separated
    • Generality of the c-Jun delta-domain requirement across targets untested
  7. 2009 High

    Defining DACH1-ERα co-occupancy and the PELP1 coactivator switch showed how hormone signaling toggles DACH1 between repression and de-repression at estrogen-response elements.

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

    PMID:19605405

    Open questions at the time
    • Mechanism of estrogen-driven corepressor disengagement not biochemically resolved
    • Direct vs indirect DACH1-PELP1 contact within ERα complex unclear
  8. 2010 High

    CAST and ChIP-seq defining a FOX-like DACH1 binding motif and FOXM1 antagonism established DACH1's intrinsic genomic targeting and a competition mechanism with forkhead factors.

    Evidence CAST, genome-wide ChIP-seq, promoter occupancy and colony formation assays

    PMID:20351289

    Open questions at the time
    • Does not show whether DACH1 and FOXM1 compete for identical sites mechanistically
    • Affinity of direct DACH1-DNA binding not quantified
  9. 2011 High

    Identifying FGF2 repression placed DACH1 upstream of a tumor-initiating cell program in glioma.

    Evidence ChIP at FGF2 locus, inducible expression, bFGF rescue, xenograft

    PMID:21750150

    Open questions at the time
    • Corepressor complex at the FGF2 locus not characterized
    • Relationship to the FGF-Dach1 developmental axis not addressed
  10. 2012 Medium

    Cell-cycle regulation in myeloid cells and a HOXA9-DACH1 leukemic complex broadened DACH1's roles to hematopoietic proliferation and context-dependent transcriptional promotion.

    Evidence Forced expression/shRNA with cell-cycle Western blots; endogenous HOXA9-DACH1 Co-IP, promoter occupancy of C/EBPα and GATA-1 at the DACH1 promoter

    PMID:22405764 PMID:22902925

    Open questions at the time
    • Single-lab, Western-blot-based cell-cycle readouts
    • Mechanism by which DACH1 activates rather than represses with HOXA9 not defined
  11. 2013 Medium

    EMT suppression via YB-1 inactivation and Wnt/TCF-LEF inhibition expanded DACH1's antitumor reach to both cytoplasmic translational control and canonical Wnt output.

    Evidence Co-IP, TCF/LEF reporter assays, Western blot for c-Myc/cyclin D1, in vivo mammary and colorectal tumor models

    PMID:24149323 PMID:24335958

    Open questions at the time
    • No direct DACH1 binding to Wnt pathway components shown
    • Cytoplasmic YB-1 mechanism not fully reconstituted
  12. 2015 High

    Defining a DACH1-SNAI1 complex at the E-cadherin E-box and CXCL5 repression mechanistically linked DACH1 to suppression of invasion and metastasis.

    Evidence Co-IP, ChIP at E-cadherin E-box, reporter assays, mouse metastasis model; gene expression screen with CXCL5 functional rescue

    PMID:25775416 PMID:25788272

    Open questions at the time
    • Selectivity for SNAI1 over SNAI2 mechanism unexplained
    • Direct vs indirect CXCL5 promoter regulation not shown
  13. 2016 High

    Showing HDAC4-mediated SUMOylation controls DACH1 stability and that stabilized DACH1 co-represses ATF6 established post-translational control of DACH1 in hepatic metabolic disease.

    Evidence Co-IP, SUMOylation assay, HDAC4 translocation assay, hepatocyte shRNA and obese mouse rescue

    PMID:27239042

    Open questions at the time
    • SUMO acceptor site on DACH1 not mapped
    • Direct DACH1 binding at the ATF6 promoter not demonstrated
  14. 2017 High

    Endothelial DACH1 control of CXCL12/CXCR4 migration under shear stress defined a flow-sensing role in coronary artery growth.

    Evidence Endothelial-specific Dach1 KO coronary morphometry, shear-stress culture, CXCR4 pharmacologic rescue

    PMID:28779009

    Open questions at the time
    • How shear stress transcriptionally regulates DACH1 is unresolved
    • Whether DACH1 directly binds the CXCL12 promoter not shown
  15. 2018 High

    Mechanisms across fibrinolysis (ATF6-tPA), MMP9 repression via p65 deacetylation, and AMPK-driven DACH1 induction integrated DACH1 into NF-κB-dependent inflammatory and coagulation control.

    Evidence Hepatocyte-specific DACH1 KO with tPA readouts; DACH1-p65/c-Jun Co-IP, MMP9 ChIP, HDAC1 recruitment and p65 acetylation assays; metformin/AMPK siRNA epistasis with CXCL1 and MDSC assays

    PMID:29900050 PMID:30504459 PMID:34772908

    Open questions at the time
    • AMPK-DACH1 connection (idx 20) is single-lab and indirect on the locus
    • How DACH1 abundance is sensed by NF-κB targets across tissues not unified
  16. 2019 Medium

    DACH1 suppression of Notch1 via c-Jun in endometrial carcinoma extended its antagonism of proliferative pathways to progestin resistance.

    Evidence Microarray, gain/loss-of-function Western blots for Notch1/c-Jun/Hes1, xenograft and progestin assays

    PMID:31215145

    Open questions at the time
    • Pathway placement is expression-based without direct promoter binding
    • Single-lab study
  17. 2020 Medium

    A DACH1-SMAD4 association controlling BMP signaling in colorectal cancer stem cells showed context-dependent, pro-stemness DACH1 output.

    Evidence DACH1-SMAD4 Co-IP, CRISPR/shRNA, intestinal organoid and xenotransplant assays

    PMID:32512510

    Open questions at the time
    • Opposing repressor vs pro-stemness roles context-dependence not mechanistically reconciled
    • Single-lab data
  18. 2021 High

    Identifying PTIP-H3K4Me3 complex recruitment as the chromatin mechanism by which DACH1 represses cell-cycle and chemotactic genes defined its epigenetic mode in kidney tubule and podocyte protection; a ciliary localization revealed a non-transcriptional function.

    Evidence Tubule- and podocyte-specific Dach1 KO/OE with disease models, DACH1 and H3K4Me3 ChIP, PTIP Co-IP, CRISPR editing of GWAS variants; siRNA knockdown with cilia imaging

    PMID:33998598 PMID:33998601 PMID:34022343

    Open questions at the time
    • How DACH1 recruitment lowers rather than raises H3K4Me3 mechanistically unresolved
    • Ciliary role (idx 28) is single-study and mechanistically uncharacterized
  19. 2023 Medium

    A Dach1-c-Jun complex repressing the pro-apoptotic gene Bim defined a cytoprotective transcriptional mechanism in pulmonary fibrosis.

    Evidence DACH1-c-Jun Co-IP, ChIP at Bim promoter, lung-specific Dach1 OE/depletion mouse models

    PMID:36754276

    Open questions at the time
    • Single-lab study
    • Corepressor machinery at the Bim promoter not defined
  20. 2024 High

    Demonstrating DACH1-driven p53 Ser392 phosphorylation, mitochondrial p53 translocation, and SLC25A37-dependent iron uptake established a transcription-independent ferroptosis axis controlled by DACH1 stability.

    Evidence CRISPR KO, DACH1-p53 Co-IP, p53 S392A mutagenesis abolishing binding, mitochondrial fractionation, hepatic fibrogenesis mouse model

    PMID:38437058

    Open questions at the time
    • How DACH1 promotes p53 Ser392 phosphorylation (direct vs via a kinase) not resolved
    • Reconciliation with DACH1's nuclear corepressor roles unaddressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DACH1 is switched between repressor, activator, and non-transcriptional (ciliary, mitochondrial-p53) functions in a tissue-specific manner, and the determinants of its complex selection, remain unresolved.
  • No unified model linking Eya-dependent switching, SUMO/ubiquitin stability control, and context-dependent partner choice
  • Structural basis of DD1 DNA binding and DS-domain corepressor docking undetermined
  • Endogenous DACH1 interactome under defined physiological states not comprehensively mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0060089 molecular transducer activity 4 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 4 GO:0005739 mitochondrion 1 GO:0005929 cilium 1
Pathway
R-HSA-162582 Signal Transduction 5 GO:0140110 transcription regulator activity 4 R-HSA-1266738 Developmental Biology 4 R-HSA-1640170 Cell Cycle 3 R-HSA-5357801 Programmed Cell Death 2
Partners
ESR1JUNNCOR1PAXIP1RELASMAD4SNAI1TP53
Complex memberships
DACH1-PTIP/H3K4Me3 complexNCoR-HDAC1/2 corepressor complexSix1-Eya-DACH transcription complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 DACH1 binds endogenous NCoR and Smad4 in cultured cells and co-localizes with NCoR in nuclear dot-like structures; the DS domain of DACH1 is sufficient for NCoR binding at a Smad4-binding site, and DACH1 repression of TGF-β-induced AP-1 and Smad signaling requires the DS domain and Smad4. Co-immunoprecipitation of endogenous proteins, co-localization by immunofluorescence, gene reporter assays, microarray analysis of endogenous TGF-β target genes, Smad4-null cell rescue experiments The Journal of Biological Chemistry High 14525983
2002 DACH1 (Dach) binds chromatin DNA directly through its conserved DD1 domain; it does not interact directly with Eya but synergizes with Eya to recruit CBP to chromatin, activating transcription via a Six-Eya-Dach complex. GST pulldown, GAL4-reporter transactivation assays, chromatin-binding assay with FLAG-Dach and GAL4-Eya fusion proteins, CBP recruitment measured on immobilized chromatin DNA template Molecular and Cellular Biology High 12215533
2003 Eya phosphatase activity switches Six1-DACH complexes from transcriptional repression to activation; DACH participates in this switch by recruiting co-activators when Eya phosphatase is present, regulating precursor cell proliferation in organogenesis. Genetic interaction studies in mice (Six1 knockout, Eya compound mutants), transcriptional reporter assays, co-immunoprecipitation, Eya phosphatase activity assays Nature High 14628042
2006 DACH1 represses cyclin D1 transcription through a c-Jun DNA-binding partner; the DS domain recruits corepressors to local chromatin. Genetic deletion studies demonstrated a requirement for cyclin D1 in DACH1-mediated inhibition of DNA synthesis, and DACH1 inhibited breast tumor growth in mice. Chromatin immunoprecipitation, reporter assays, cyclin D1 knockout rescue experiments, colony formation/Matrigel growth assays, xenograft tumor growth in mice Molecular and Cellular Biology High 16980615
2006 DACH1 binds c-Jun and inhibits AP-1 transcriptional activity; it coprecipitates HDAC1, HDAC2, and NCoR and represses c-Jun target genes through the c-Jun delta domain in a manner requiring the conserved DS domain. An oncogenic v-Jun deleted of the delta domain is resistant to DACH1 repression. Co-immunoprecipitation, reporter assays, Cre-mediated c-jun excision in c-jun(fl/fl) cells (epistasis), c-jun rescue of DACH1 inhibition, domain deletion mutagenesis Molecular Biology of the Cell High 17182846
2009 DACH1 binds ERα by co-immunoprecipitation and co-associates with ERα at endogenous ER response elements by ChIP; it inhibits ERα transcriptional activity requiring the conserved DS domain. PELP1 was identified as a DACH1 C-terminus binding protein by proteomics; estrogen recruits ERα and disengages corepressors from DACH1, allowing PELP1 to serve as ERα coactivator. Co-immunoprecipitation/Western blot, chromatin immunoprecipitation, reporter assays, proteomic identification of PELP1, domain deletion mutagenesis Cancer Research High 19605405
2010 DACH1 binds a DNA sequence resembling the FOX (Forkhead) binding site identified by CAST; genome-wide ChIP-seq confirmed DACH1 occupancy at FOX-like elements. DACH1 antagonized FOXM1 target gene expression and promoter occupancy in chromatin, blocking contact-independent growth. Cyclic amplification and selection of targets (CAST), in silico promoter analysis, ChIP coupled with high-throughput sequencing (ChIP-seq), promoter occupancy assays, colony formation assay Proceedings of the National Academy of Sciences of the USA High 20351289
2013 DACH1 suppresses EMT by repressing cytoplasmic translational induction of Snail through inactivating YB-1, and in the nucleus DACH1 antagonizes YB-1-mediated oncogenic transcriptional modules; DACH1 blocked YB-1-induced mammary tumor growth and EMT in mice. Co-immunoprecipitation, reporter assays, in vivo mammary tumor model, knockdown/overexpression studies Cancer Research Medium 24335958
2015 DACH1 physically interacts with SNAI1 (but not SNAI2) and forms a complex that binds the E-box on the E-cadherin promoter in an SNAI1-dependent manner; this complex inhibits SNAI1 transcriptional activity, resulting in E-cadherin activation and suppression of breast cancer EMT and metastasis. Co-immunoprecipitation, chromatin immunoprecipitation at E-cadherin E-box, reporter assays, loss/gain-of-function experiments, mouse metastasis model Oncogenesis High 25775416
2004 Chick Dach1 interacts with the Smad complex and Sin3a corepressor to repress BMP-mediated transcription; this antagonism regulates AER formation and limb proximodistal patterning. Co-immunoprecipitation (Dach1-Smad complex and Sin3a), in vivo gain/loss-of-function in chick limb, reporter assays Development High 15280207
2016 In obesity, CaMKII phosphorylates HDAC4 blocking its nuclear translocation; this decreases HDAC4-mediated SUMOylation of DACH1, protecting DACH1 from proteasomal degradation. Stabilized DACH1 then co-represses ATF6 transcription together with NCOR, leading to PERK-TRB3 pathway activation and defective hepatocyte insulin signaling. Co-immunoprecipitation (DACH1-NCOR complex), SUMOylation assay, HDAC4 nuclear translocation assay, shRNA knockdown in liver (hepatocyte-specific), obese mouse model rescue experiments, Western blot Cell Reports High 27239042
2018 DACH1 represses ATF6 transcription in hepatocytes (together with NCOR), controlling hepatocyte-derived tPA and basal plasma tPA/fibrinolytic activity; hepatocyte-DACH1-knockout mice show increased liver Plat, circulating tPA, and altered coagulation parameters reversed by hepatocyte Plat silencing. Hepatocyte-specific DACH1 knockout mice, co-repressor assays, liver Plat/tPA measurements, bleeding/thrombosis time assays, hepatocyte-ATF6 knockout comparison Blood High 30504459
2011 DACH1 transcriptionally represses FGF2/bFGF; ChIP confirmed DACH1 binding at the FGF2 locus in serum-free glioma cells. Exogenous bFGF rescued spheroid-forming activity and tumorigenicity of DACH1-high glioma cells, placing DACH1 upstream of FGF2 in control of tumor-initiating cell activity. Chromatin immunoprecipitation, gene expression analysis, inducible DACH1 expression system (doxycycline-regulated), exogenous bFGF rescue, in vivo subcutaneous xenograft Proceedings of the National Academy of Sciences of the USA High 21750150
2017 Endothelial DACH1 stimulates CXCL12 expression and endothelial cell polarization/migration against flow; loss of Dach1 in endothelium resulted in small coronary arteries and reduced CXCR4-dependent cell migration. High uniform laminar shear stress down-regulates DACH1 while low variable flow maintains it, linking flow quality to artery growth. Endothelial-specific Dach1 knockout mice (in vivo coronary artery morphometry), DACH1 overexpression under shear stress in culture, CXCL12/CXCR4 pharmacological inhibition rescue, flow cytometry, immunofluorescence Genes & Development High 28779009
2021 DACH1 controls kidney tubule cell-cycle and myeloid chemotactic factor expression; tubule-specific Dach1 deletion caused more severe renal fibrosis in multiple injury models, while overexpression was protective. DACH1 interacts with PTIP (a component of the H3K4Me3 complex) and recruits it to DACH1-bound promoters, repressing target gene transcription and reducing promoter H3K4Me3 levels. Tubule-specific Dach1 KO and overexpression mouse models, single-cell RNA-seq, chromatin immunoprecipitation (ChIP for DACH1 and H3K4Me3), CRISPR-Cas9 gene editing of GWAS risk variants, in silico promoter analysis, PTIP co-immunoprecipitation The Journal of Clinical Investigation High 33998598
2021 Podocyte-specific DACH1 interacts with PTIP (an H3K4Me3 complex component) and recruits it to promoter-binding sites, repressing transcription and reducing H3K4Me3 at target promoters; DACH1 knockdown combined with hyperglycemia triggers target gene upregulation and increased promoter H3K4Me3. Podocyte-specific Dach1 KO mice develop accelerated injury after diabetes onset while DACH1 augmentation is protective. Podocyte-specific Dach1 KO and overexpression mice, RNA-seq, ChIP (H3K4Me3), Co-IP of PTIP-DACH1, high-throughput in silico promoter analysis, diabetic kidney disease models The Journal of Clinical Investigation High 33998601
2012 DACH1 regulates cell cycle progression in myeloid progenitor cells: forced DACH1 expression induced p27(Kip1) and repressed p21(Cip1), increased cyclin D1/D3/F and Cdk 1/4/6 expression; DACH1 knockdown blocked HL-60 cell cycle progression through decrease of cyclins/Cdks, increase of p21(Cip1), and reduced Rb phosphorylation. Forced expression and shRNA knockdown in myeloid progenitor/HL-60 cells, Western blot for cell cycle proteins, Rb phosphorylation assay Biochemical and Biophysical Research Communications Medium 22405764
2012 An endogenous HOXA9-DACH1 complex is mediated by the carboxyl terminus of DACH1 in t(9;11) leukemia cells; DACH1 has stronger transcription-promoting activity with HOXA9 than does PBX2 with HOXA9; C/EBPα and GATA-1 directly bind the DACH1 promoter and act as transcriptional suppressors of DACH1. Co-immunoprecipitation of endogenous HOXA9-DACH1, qRT-PCR, chromatin occupancy of C/EBPα/GATA-1 at DACH1 promoter, domain mapping (DACH1 carboxyl terminus), ectopic expression experiments Biochemical and Biophysical Research Communications Medium 22902925
2018 DACH1 inhibits the transcription of MMP9 by interacting with p65 and c-Jun at NF-κB and AP-1 binding sites in the MMP9 promoter; DACH1-p65 association promotes recruitment of HDAC1 to the NF-κB site, reducing p65 acetylation and transcriptional activity, thereby decreasing MMP9 levels and breast cancer cell invasion. Co-immunoprecipitation (DACH1-p65, DACH1-c-Jun), chromatin immunoprecipitation at MMP9 promoter NF-κB/AP-1 sites, HDAC1 recruitment assay, p65 acetylation assay, invasion assays Cell Death Discovery High 34772908
2015 DACH1 suppresses CXCL5 expression in lung adenocarcinoma cells; there is an inverse correlation between DACH1 mRNA and CXCL5 in lung cancer cell lines and human NSCLC tissues, and functional rescue showed DACH1 effects on invasion are dependent in part on CXCL5 suppression. Unbiased gene expression screen, qPCR correlation analysis, functional rescue with CXCL5 overexpression, in vitro migration/invasion assays, in vivo tumor xenograft Oncotarget Medium 25788272
2018 Metformin enhances AMPK phosphorylation, which induces DACH1 expression leading to NF-κB inhibition and reduced CXCL1 secretion; DACH1 knockdown blocked the effect of metformin on MDSC chemotaxis, placing DACH1 downstream of AMPK and upstream of CXCL1/NF-κB in this pathway. Metformin treatment with AMPK/DACH1 knockdown (siRNA epistasis), CXCL1 secretion assay, MDSC migration assay, tumor xenograft in mice with adoptive transfer Oncoimmunology Medium 29900050
2013 DACH1 suppresses colorectal cancer growth by inhibiting Wnt/TCF-LEF signaling; re-expression of DACH1 reduced TCF/LEF luciferase reporter activity and suppressed Wnt downstream targets c-Myc and cyclin D1. DACH1 re-expression induced G2/M phase arrest and sensitized cells to docetaxel. TCF/LEF reporter assay, Western blot for c-Myc/cyclin D1, cell cycle analysis (flow cytometry), xenograft tumor model, 5-aza-dC demethylation/re-expression Epigenetics Medium 24149323
2020 DACH1 promotes colorectal cancer stem cell properties through suppression of BMP signaling via SMAD4; co-immunoprecipitation demonstrated association between DACH1 and SMAD4; shRNA-mediated DACH1 suppression reduced organoid formation and tumor growth, while DACH1 overexpression stimulated colonsphere formation in the context of dysregulated BMP signaling. Co-immunoprecipitation (DACH1-SMAD4), CRISPR/Cas9 KO and shRNA knockdown, intestinal organoid model, microarray data analysis, xenotransplant EBioMedicine Medium 32512510
2018 DACH1 and SIX1 co-localize in hepatocellular carcinoma cells; immunoprecipitation shows DACH1 (Flag-tagged) pulls down p53 and SIX1, while SIX1 (His-tagged) pulls down DACH1 but not p53 (indicating SIX1-p53 regulation is indirect through DACH1). DACH1 overexpression suppresses tumorigenesis by up-regulating p53. Immunoprecipitation (tagged proteins), immunofluorescence co-localization, colony formation assay, nude mice xenograft, Western blot for p53 Cancer Biology & Therapy Medium 29333942
2002 Mutations in the EYA domain of Eya1 associated with BOR syndrome (S486P and L504R) show defective interactions with Dach1, G proteins, and some Six proteins by GST pulldown and mammalian two-hybrid assays, implicating direct Eya1-Dach1 protein interaction in normal development. Mammalian two-hybrid assay, GST pulldown, trypsin/V8 protease digestion pattern analysis, transcriptional activation assay (myogenin promoter) Journal of Human Genetics Medium 11950062
2024 DACH1 modulates ferroptosis via the P53/SLC25A37 pathway: ferroptosis inducers increase DACH1 protein by suppressing ubiquitin-proteasome degradation; DACH1 induces p53 phosphorylation at serine 392, causing mitochondrial translocation of p53; mitochondrial p53 binds SLC25A37, enhancing mitochondrial iron uptake and triggering ferroptosis. Mutation of serine 392 prevents DACH1-p53 binding and ferroptosis. CRISPR-Cas9 DACH1 knockout in hepatic stellate cells, Co-immunoprecipitation (DACH1-p53), pulldown assays, p53 S392A mutagenesis, mitochondrial fractionation, mouse model of hepatic fibrogenesis with HSC-specific knockdowns Hepatology Communications High 38437058
2023 Dach1 combined with c-Jun protooncogene selectively binds the promoter of the pro-apoptotic gene Bim, repressing its expression and protecting type II alveolar epithelial cells from apoptosis in pulmonary fibrosis. Co-immunoprecipitation (DACH1-c-Jun), ChIP at Bim promoter, lung-specific Dach1 overexpression and Dach1 depletion mouse models (BLM-induced PF), in vitro apoptosis assay Translational Research Medium 36754276
2019 DACH1 suppresses EMT and progestin resistance in endometrial carcinoma through Notch1 pathway inhibition via c-Jun; DACH1 overexpression decreased c-Jun, Notch1, and Hes1 expression, and reversed progestin resistance both in vitro and in a xenograft model. Microarray analysis, gain/loss-of-function with Western blot for Notch1/c-Jun/Hes1, xenograft model, progestin sensitivity assays Cancer Medicine Medium 31215145
2021 siRNA-mediated depletion of DACH1 disrupted primary cilia formation and function in human cells; DACH1 protein localizes to the base of primary cilia as shown by advanced microscopy, revealing a role for DACH1 in ciliogenesis. siRNA knockdown of DACH1, advanced microscopy imaging (localization at base of cilia), cilia functional assays Genomics Medium 34022343
2008 Dach1 and Dach2 are redundantly required for Müllerian duct development; Dach1/2 double mutants show severely disrupted female reproductive tract with abnormal Lim1 and Wnt7a expression in the Müllerian duct, while Wolffian duct development is unaffected. Dach1/Dach2 double homozygous knockout mice, in situ hybridization for Lim1 and Wnt7a in Müllerian duct Genesis Medium 18395837
2002 Fibroblast growth factors (FGF1, 2, 8, 9 but not FGF10) up-regulate Dach1 expression in mouse limb buds while BMP4 down-regulates it; FGF4 or FGF8 can substitute for the apical ectodermal ridge in maintaining Dach1 expression, placing Dach1 as a downstream target of FGF signaling in skeletal development. FGF-bead implantation in ex vivo mouse limb bud organ culture, BMP4/Shh bead implantation, AER removal with FGF rescue, immunolocalization of Dach1 with Runx2 and CDK inhibitors Developmental Dynamics Medium 12203718

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 535 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 126 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 124 12215533
2006 DACH1 is a cell fate determination factor that inhibits cyclin D1 and breast tumor growth. Molecular and cellular biology 109 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 79 24149323
2015 DACH1 inhibits SNAI1-mediated epithelial-mesenchymal transition and represses breast carcinoma metastasis. Oncogenesis 78 25775416
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 The DACH/EYA/SIX gene network and its role in tumor initiation and progression. International journal of cancer 75 26096807
2013 Cell fate factor DACH1 represses YB-1-mediated oncogenic transcription and translation. Cancer research 69 24335958
2021 Transcriptome-wide association analysis identifies DACH1 as a kidney disease risk gene that contributes to fibrosis. The Journal of clinical investigation 67 33998598
2006 Cell fate determination factor DACH1 inhibits c-Jun-induced contact-independent growth. Molecular biology of the cell 66 17182846
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) 49 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
2009 Altered expression of DACH1 and cyclin D1 in endometrial cancer. Cancer biology & therapy 46 19502783
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
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 44 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
2017 BMP6 Regulates Proliferation and Apoptosis of Human Sertoli Cells Via Smad2/3 and Cyclin D1 Pathway and DACH1 and TFAP2A Activation. Scientific reports 39 28387750
2015 MiR-217 Promotes Tumor Proliferation in Breast Cancer via Targeting DACH1. Journal of Cancer 38 25653720
2021 DACH1 protects podocytes from experimental diabetic injury and modulates PTIP-H3K4Me3 activity. The Journal of clinical investigation 37 33998601
2021 Dach1 Extends Artery Networks and Protects Against Cardiac Injury. Circulation research 37 34383559
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
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
2017 PtI2(DACH), the iodido analogue of oxaliplatin as a candidate for colorectal cancer treatment: chemical and biological features. Dalton transactions (Cambridge, England : 2003) 35 28229139
2014 Epigenetic silencing of DACH1 induces the invasion and metastasis of gastric cancer by activating TGF-β signalling. Journal of cellular and molecular medicine 35 24912879
2019 Cyclometalated Gold(III) Complexes Bearing DACH Ligands. Inorganic chemistry 34 31247820
2017 DACH1 suppresses breast cancer as a negative regulator of CD44. Scientific reports 33 28659634
2008 Mouse Dach1 and Dach2 are redundantly required for Müllerian duct development. Genesis (New York, N.Y. : 2000) 33 18395837
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
2001 DACH: genomic characterization, evaluation as a candidate for postaxial polydactyly type A2, and developmental expression pattern of the mouse homologue. Genomics 33 11543628
2018 SIX1 and DACH1 influence the proliferation and apoptosis of hepatocellular carcinoma through regulating p53. Cancer biology & therapy 32 29333942
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 32 12898627
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
2019 Regulation of cancer stem cell properties by SIX1, a member of the PAX-SIX-EYA-DACH network. Advances in cancer research 30 30691681
2018 An ATF6-tPA pathway in hepatocytes contributes to systemic fibrinolysis and is repressed by DACH1. Blood 30 30504459
2014 Silencing DACH1 promotes esophageal cancer growth by inhibiting TGF-β signaling. PloS one 30 24743895
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
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 29 22405764
1997 [Oxaliplatin: the first DACH platinum in clinical practice]. Bulletin du cancer 29 9295871
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 25 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
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 23 30720199
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
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
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 17 32408786
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
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 15 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
2021 Role of DACH1 on Proliferation, Invasion, and Apoptosis in Human Lung Adenocarcinoma Cells. Current molecular medicine 9 33463463
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 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
2017 Probing the Interactions of Cytotoxic [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)] and Its PtIV Derivatives with Human Serum. ChemMedChem 7 28206707

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