Affinage

BACH1

Transcription regulator protein BACH1 · UniProt O14867

Length
736 aa
Mass
82.0 kDa
Annotated
2026-06-09
100 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BACH1 is a heme-regulated BTB-bZIP transcription factor that operates principally as a sequence-specific repressor by heterodimerizing with small Maf proteins and binding Maf recognition elements (MAREs), most paradigmatically at the heme oxygenase-1 (HO-1/HMOX1) enhancer (PMID:12356737). Intracellular heme directly binds BACH1 — five heme molecules coordinate per monomer through C-terminal CP (cysteine-proline) motifs in two distinct configurations that differentially control DNA binding and nuclear export — abrogating its repressor activity and de-repressing antioxidant targets in a substrate-controlled feedback loop (PMID:12356737, PMID:17701549). BACH1 is a rate-limiting and remarkably specific switch for free heme, with its loss almost exclusively inducing HMOX1 (PMID:18550526), and it is also inactivated by oxidant-driven sulfhydryl oxidation (PMID:18550526). Heme- and oxidation-triggered turnover proceeds through two complementary degrons encrypted in the homodimeric BTB domain, recognized sequentially by the F-box ligases FBXO22 and FBXL17, whereas Nrf2-driven HO-1 induction depletes heme to stabilize BACH1, creating a Nrf2→HO-1→heme→FBXO22→BACH1 axis that promotes metastasis (PMID:31257023, PMID:39504958); deubiquitination by USP14 provides an opposing stabilizing input (PMID:37229827). Beyond oxidative-stress control, BACH1 rewires cancer metabolism by transcriptionally activating glycolytic enzymes HK2 and GAPDH while repressing electron-transport-chain genes, shifting cells toward glycolysis and modulating sensitivity to ETC inhibitors (PMID:31257027, PMID:30842661). It also acts as a broad transcriptional regulator of pro-metastatic, pro-angiogenic, and developmental programs: it represses Wnt/β-catenin targets via direct BTB-domain binding to TCF4 and recruitment of HDAC1 (PMID:26123998, PMID:31911270), suppresses epithelial-adhesion and antioxidant/ferroptosis programs (FOXA1, claudins, SCD1, glutathione and Gpx4 genes) (PMID:31919242, PMID:36670112, PMID:38066332), and partners with YAP, G9a, ATF4, and HMGA2 to drive endothelial inflammation, vascular smooth-muscle phenotypic switching, and EMT (PMID:35196865, PMID:36864760, PMID:38838145, PMID:30654010). In stem cells BACH1 scaffolds OCT4/SOX2/NANOG together with MLL/SET1 and PRC2 to maintain pluripotency-associated chromatin states (PMID:30891497, PMID:33503260). Distinct from these transcriptional roles, BACH1 (FANCJ/BRIP1) is a DNA-dependent ATPase and 5'-to-3' DNA helicase that interacts with the BRCA1 BRCT repeats and, via S-phase phosphorylation at Thr1133, with TopBP1 to support double-strand-break repair, RPA loading, and ATR-dependent replication checkpoint activation (PMID:14983014, PMID:16462773, PMID:20159562). Helicase-defective germline BACH1 variants associate with early-onset breast cancer (PMID:14983014).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 High

    Established BACH1's core identity as a heme-sensing transcriptional repressor, answering how the cell links free heme levels to antioxidant gene expression.

    Evidence In vitro MARE-binding, reporter assays, Bach1 knockout and Bach1/Nrf2 compound mice, and ChIP at HO-1 enhancers

    PMID:12356737

    Open questions at the time
    • Did not resolve the structural basis of heme-induced loss of DNA binding
    • Scope of BACH1-regulated genes beyond HO-1 unaddressed
  2. 2004 High

    Defined a wholly separate enzymatic function for the same protein as a DNA helicase in BRCA1-dependent repair, and linked helicase-defective variants to cancer predisposition.

    Evidence Reconstituted in vitro ATPase/helicase assays, BRCA1-BRCT interaction studies, and patient-derived mutant analysis

    PMID:14983014

    Open questions at the time
    • Relationship between the helicase and transcription-factor activities unresolved
    • Substrate range of the helicase in vivo not defined
  3. 2006 High

    Placed BACH1 functionally within the DNA-damage response by showing it is required for efficient repair and for concentrating BRCA1 at damage foci.

    Evidence BACH1-deficient cells, γ-H2AX co-localization, BRCA1 foci quantification, and repair assays

    PMID:16462773

    Open questions at the time
    • Kinase responsible for damage-induced BACH1 phosphorylation not identified here
    • How BACH1 loss reduces BRCA1 foci without disrupting the complex unclear
  4. 2007 High

    Resolved the molecular basis of heme sensing by mapping multiple CP-motif heme-binding sites with distinct coordination chemistries controlling DNA binding versus export.

    Evidence Heme titration, UV-vis and resonance Raman spectroscopy, and CP-motif mutagenesis

    PMID:17701549

    Open questions at the time
    • In vivo occupancy of the five sites under physiological heme not established
    • Link between specific sites and downstream degradation pathways unaddressed
  5. 2010 High

    Extended the helicase function into the replication checkpoint, showing phospho-Thr1133-dependent recruitment of TopBP1 enables RPA loading and ATR signaling.

    Evidence Co-IP with phospho-site mapping, chromatin fractionation for RPA loading, and ATR checkpoint phosphorylation assays

    PMID:20159562

    Open questions at the time
    • S-phase kinase phosphorylating Thr1133 not pinned down
    • Whether helicase catalysis is required for checkpoint role untested
  6. 2008 Medium

    Demonstrated BACH1 acts as a highly specific heme rheostat, with its inactivation by oxidants being necessary and sufficient for HMOX1 induction.

    Evidence siRNA knockdown, genome-wide microarray, reporter assays, and arsenite dose-response in keratinocytes

    PMID:18550526

    Open questions at the time
    • Specific oxidized cysteines not mapped
    • Specificity may be cell-type dependent
  7. 2015 High

    Revealed a non-MARE, protein-protein repression mode in which the BTB domain binds TCF4 and recruits HDAC1 to silence Wnt/β-catenin angiogenic targets.

    Evidence Co-IP, GST pull-down, ChIP, domain-deletion mutants, and hindlimb ischemia model

    PMID:26123998 PMID:31911270

    Open questions at the time
    • Whether heme regulates this TCF4 interaction unknown
    • Generality across vascular beds not established
  8. 2019 High

    Identified FBXO22 as the heme-induced E3 ligase degrading BACH1 and embedded BACH1 in a Nrf2→HO-1→heme→BACH1 metastasis axis.

    Evidence Reciprocal Co-IP, multiple KO mouse models, pharmacological HO-1 inhibition, and human lung cancer specimens

    PMID:31257023

    Open questions at the time
    • Degron architecture not yet defined at this stage
    • Other ligases contributing to turnover not excluded
  9. 2019 High

    Showed BACH1 reprograms cancer metabolism, activating HK2/GAPDH glycolysis and repressing ETC genes, with antioxidants stabilizing BACH1 to drive metastasis and metformin sensitivity.

    Evidence Knockdown/overexpression, glucose-uptake/lactate assays, heme-resistant mutant rescue, RNA-seq, and xenograft/metastasis models

    PMID:30842661 PMID:31257027

    Open questions at the time
    • Direct vs indirect activation of glycolytic genes not fully separated
    • Tissue-specific metabolic outputs incompletely mapped
  10. 2019 Medium

    Implicated BACH1 as a pluripotency scaffold, stabilizing OCT4/SOX2/NANOG via USP7 and recruiting PRC2 to repress differentiation genes.

    Evidence Co-IP, ChIP, H3K27me3 occupancy, and BACH1 knockout in hESCs

    PMID:30891497 PMID:33503260

    Open questions at the time
    • How a repressor coordinates both PRC2 and activating MLL/SET1 complexes mechanistically unclear
    • Heme dependence of stem-cell scaffolding untested
  11. 2022 High

    Connected BACH1 to vascular pathology through YAP and G9a partnerships driving endothelial inflammation and VSMC phenotypic switching.

    Evidence Cell-type-specific Bach1 KO mice, ChIP, Co-IP, ATAC-seq, and rescue experiments

    PMID:35196865 PMID:36864760

    Open questions at the time
    • Whether YAP and G9a act in a single complex or separate contexts unresolved
    • Heme regulation of these activities unaddressed
  12. 2023 High

    Expanded BACH1 into metabolic and inflammatory signaling, showing it suppresses hepatic insulin signaling via PTP1B/IR-β and represses antioxidant/ferroptosis programs during infection.

    Evidence Co-IP, hepatocyte- and whole-animal Bach1 KO/OE models, glucose/insulin tests, Mtb infection models, and scRNA-seq

    PMID:38066332 PMID:38129407

    Open questions at the time
    • Mechanism of BACH1 enabling PTP1B-IRβ docking not structurally defined
    • Direct vs indirect repression of glutathione/Gpx4 genes incompletely resolved
  13. 2024 High

    Provided the structural logic of BACH1 degradation, showing two BTB-domain degrons read sequentially by FBXO22 and FBXL17 to couple oxidative state to turnover.

    Evidence Structural studies, BTB-interface mutagenesis, reconstituted ubiquitination, and oxidative-stress perturbations

    PMID:39504958

    Open questions at the time
    • In vivo hierarchy of the two ligases across tissues not established
    • How transcriptional co-repressor occupancy masks the first degron mechanistically incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BACH1's two activities — heme-sensing transcription factor and DNA helicase — are integrated within a single cell, and whether heme or redox state coordinates its diverse context-specific partnerships, remains unresolved.
  • No unified model linking helicase/repair function with transcriptional regulation
  • Determinants selecting among the many described partners (TCF4, YAP, G9a, ATF4, PTP1B, OSN) in a given cell type unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 2 GO:0008289 lipid binding 2 GO:0060090 molecular adaptor activity 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-73894 DNA Repair 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-5357801 Programmed Cell Death 2
Partners
BRCA1FBXL17FBXO22HDAC1MAFKTCF4TOPBP1YAP1

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 BACH1 acts as a transcriptional repressor of heme oxygenase-1 (HO-1) by forming heterodimers with small Maf proteins (e.g., MafK) and binding to Maf recognition elements (MAREs) in HO-1 enhancers; heme directly binds BACH1 and abrogates its DNA-binding activity, causing nuclear export and de-repression of HO-1 in a feedback loop where the substrate (heme) controls the repressor. In vitro MARE-binding assays, reporter gene assays, gene targeting in mice (Bach1 knockout), Bach1/Nrf2 compound-deficient mouse analysis, chromatin immunoprecipitation (ChIP) The EMBO journal High 12356737
2004 BACH1 (FANCJ/BRIP1) is a DNA-dependent ATPase and 5'-to-3' DNA helicase; germline BACH1 coding-sequence changes found in early-onset breast cancer patients produce proteins defective in helicase activity, and BACH1 directly interacts with the BRCT repeats of BRCA1 to support double-strand break repair. In vitro ATPase and helicase assays, direct protein interaction studies, analysis of patient-derived mutant proteins Proceedings of the National Academy of Sciences of the United States of America High 14983014
2007 BACH1 contains multiple heme-binding sites: five heme molecules bind per BACH1 monomer with two distinct coordination structures. Mutagenesis established that four CP (cysteine-proline) motifs in the C-terminus each coordinate one heme molecule, and the two types of heme-binding sites differentially regulate DNA-binding and nuclear export activities. Heme-titration assay, UV-visible and resonance Raman spectroscopy of BACH1-heme complexes, site-directed mutagenesis of CP motifs IUBMB life High 17701549
2006 BACH1 is required for efficient DNA double-strand break repair and for localizing BRCA1 to DNA damage foci; following DNA damage BACH1 is phosphorylated, forms nuclear foci colocalizing with γ-H2AX, and loss of BACH1 diminishes intensity of BRCA1 foci without disrupting the BACH1/BRCA1 complex. BACH1-deficient cell lines, immunofluorescence co-localization with γ-H2AX, analysis of BRCA1 foci by immunostaining, DNA repair assays Oncogene High 16462773
2006 CoPP induces HO-1 by accelerating proteasomal degradation of BACH1 protein (half-life reduced from 19 h to 2.8 h) and by stabilizing Nrf2 protein; silencing BACH1 with siRNA alone is sufficient to increase HO-1 mRNA and protein, establishing BACH1 as a rate-limiting post-transcriptional regulator of HO-1. siRNA knockdown of BACH1 and Nrf2, protein half-life measurement by cycloheximide chase, Western blot, qRT-PCR in Huh-7 cells FASEB journal Medium 17065227
2008 BACH1 is inactivated at low micromolar arsenite concentrations through sulfhydryl oxidation, and BACH1 inactivation is necessary and sufficient for HMOX1 transcriptional induction; genome-wide expression profiling after BACH1 siRNA knockdown showed that loss of BACH1 almost exclusively induces HMOX1, indicating BACH1 acts as a highly specific rheostat for intracellular free heme. siRNA knockdown, genome-wide expression microarray, reporter assays, arsenite dose-response in human keratinocytes The Journal of biological chemistry Medium 18550526
2010 BACH1/FANCJ interacts specifically with TopBP1 via S-phase-specific phosphorylation of BACH1 at Thr1133 and the C-terminal tandem BRCT domains of TopBP1; both TopBP1 and BACH1 are required for RPA loading onto chromatin and for ATR-dependent phosphorylation events after replication stress, placing BACH1 in an early role in the replication checkpoint. Co-immunoprecipitation, phosphorylation-specific interaction mapping, chromatin fractionation (RPA loading), ATR checkpoint phosphorylation assays after siRNA depletion Molecular cell High 20159562
2015 BACH1 directly binds TCF4 (via residues 81–89 of the BTB domain) and reduces β-catenin/TCF4 interaction; BACH1 also reduces p300/CBP interaction with β-catenin and β-catenin acetylation, and recruits histone deacetylase 1 (HDAC1) to the TCF4-binding site of the IL-8 promoter, thereby repressing Wnt/β-catenin target gene transcription and angiogenesis. Co-immunoprecipitation, GST pull-down, chromatin immunoprecipitation (ChIP), reporter assays, domain-deletion mutants, hindlimb ischemia mouse model Circulation research High 26123998
2019 Heme triggers proteasomal degradation of BACH1 by promoting its interaction with the F-box ubiquitin ligase FBXO22; Nrf2 accumulation stabilizes BACH1 by inducing HO-1 (which catabolizes heme), thereby forming a Nrf2→HO-1→heme depletion→BACH1 stabilization→metastasis axis in lung cancer. Co-immunoprecipitation of BACH1 with FBXO22, genetic mouse models (Keap1 KO, Fbxo22 KO, BACH1 KO), pharmacological HO-1 inhibition, human lung cancer specimens Cell High 31257023
2019 Antioxidants (N-acetylcysteine, vitamin E) stabilize BACH1 by reducing free heme levels; stabilized BACH1 transcriptionally activates Hexokinase 2 (HK2) and GAPDH, increasing glucose uptake, glycolysis rates, and lactate secretion to drive lung cancer metastasis. BACH1 genetic knockdown/overexpression, glucose uptake and lactate secretion assays, gene expression analysis, mouse lung cancer metastasis models, antioxidant treatment paradigms Cell High 31257027
2019 BACH1 decreases glucose utilization in the TCA cycle and negatively regulates transcription of electron transport chain (ETC) genes in breast cancer cells; BACH1 depletion or hemin-mediated degradation sensitizes cells to ETC inhibitors (e.g., metformin), and a heme-resistant BACH1 mutant rescues resistance to metformin. shRNA knockdown, hemin-induced degradation, heme-resistant BACH1 mutant overexpression, cell line and patient-derived xenograft growth assays, metformin sensitivity assays, RNA-seq Nature High 30842661
2019 BACH1 interacts with Nanog, Sox2, and Oct4 in human embryonic stem cells and facilitates their deubiquitination and stabilization by recruiting deubiquitinase USP7; BACH1 also interacts with PRC2 and recruits it to mesendodermal gene promoters, repressing differentiation and maintaining pluripotency. Co-immunoprecipitation, ChIP, siRNA knockdown, BACH1 knockout in hESCs, H3K27me3 occupancy analysis Science advances Medium 30891497
2020 BACH1 directly represses FOXA1 (an activator of CDH1/E-cadherin) and epithelial cell-adhesion genes CLDN3 and CLDN4, thereby promoting epithelial-to-mesenchymal transition and metastasis in pancreatic cancer; BACH1 binds the FOXA1 promoter as established by ChIP. BACH1 knockdown and overexpression, ChIP, orthotopic mouse implantation model, immunohistochemistry with anti-BACH1 mAb Cancer research Medium 31919242
2021 BACH1 directly interacts with OCT4/SOX2/NANOG and MLL/SET1 histone methyltransferase complexes via its BTB and bZIP domains; BACH1 loss reduces NANOG and MLL1/SET1 occupancy on chromatin and decreases H3K4me3 at promoters and enhancers of pluripotency genes, implicating BACH1 as a chromatin scaffold maintaining enhancer activity. Co-immunoprecipitation, ChIP, domain-deletion mutant analysis, H3K4me3 chromatin profiling, chromatin looping assays in mouse ESCs Nucleic acids research High 33503260
2022 BACH1 upregulates YAP expression by binding to the YAP promoter, and BACH1 forms a complex with YAP that drives transcription of endothelial adhesion molecules (ICAM1, VCAM1) in response to oscillatory shear stress or TNF-α, promoting atherosclerosis; endothelial-specific Bach1 deletion reduces lesion formation in mice. EC-specific Bach1 KO mouse atherosclerosis models, ChIP (BACH1 binding to YAP promoter), Co-immunoprecipitation (BACH1-YAP complex), YAP overexpression rescue experiments Circulation research High 35196865
2022 BACH1 suppresses chromatin accessibility at promoters of VSMC marker genes by recruiting histone methyltransferase G9a and cofactor YAP, maintaining H3K9me2 repressive marks and thereby driving VSMC phenotypic switching from contractile to synthetic state; VSMC-specific Bach1 loss inhibits neointima formation after wire injury. VSMC-specific Bach1 KO mice, wire injury model, ATAC-seq (chromatin accessibility), ChIP (G9a, H3K9me2), siRNA knockdown of G9a and YAP Nucleic acids research High 36864760
2023 BACH1 directly interacts with protein-tyrosine phosphatase 1B (PTP1B) and insulin receptor β (IR-β); loss of BACH1 reduces PTP1B/IR-β interaction upon insulin stimulation and enhances insulin signaling, establishing a mechanism by which BACH1 suppresses hepatic insulin signaling and glucose homeostasis. Co-immunoprecipitation of BACH1 with PTP1B and IR-β, hepatocyte-specific Bach1 KO and overexpression mouse models, insulin tolerance and glucose tolerance tests, PTP1B inhibition rescue experiments Nature communications High 38129407
2024 BACH1 contains two distinct ubiquitin-dependent degrons encrypted in the quaternary structure of its homodimeric BTB domain: (1) a degron at the BTB dimer interface, unmasked from transcriptional co-repressors after oxidative stress releases BACH1 from chromatin, recognized by FBXO22; (2) a second degron manifested by destabilized BTB dimers under oxidation, recognized by a pair of FBXL17 proteins that remodels BACH1 into E3-bound monomers for ubiquitination. The two E3 ligases act in a complementary, sequential manner. Structural studies, mutagenesis of BTB domain interface, biochemical reconstitution of E3 ligase substrate interactions, ubiquitination assays, oxidative stress perturbations Cell High 39504958
2004 Transgenic overexpression of BACH1 in megakaryocytes (under GATA-1 regulatory control) causes thrombocytopenia and impaired megakaryocyte maturation; BACH1 binds to the thromboxane synthase gene (a p45/NF-E2 target) and represses MARE-dependent transcription in megakaryocytes, competing with p45. Transgenic mouse generation, ChIP (BACH1 binding to thromboxane synthase gene), platelet counts, megakaryocyte ploidy analysis, gene expression of p45 target genes Blood Medium 15613547
2010 BACH1 specifically and critically represses HO-1 in keratinocytes; Bach1 siRNA depletion or genetic deletion markedly increases HO-1 expression at baseline, while BACH1 overexpression abolishes H2O2-induced HO-1 induction; however, during keratinocyte differentiation, HO-1 induction is BACH1-independent (Bach1 overexpression does not block differentiation-associated HO-1). siRNA knockdown, Bach1 knockout keratinocytes, BACH1 overexpression, HO-1 reporter and mRNA assays, ROS measurement The Journal of biological chemistry Medium 20501657
2018 BACH1 promotes erythroid commitment at the erythro-myeloid bifurcation by repressing C/EBPβ expression and its myeloid target genes, binding to regulatory regions co-bound by C/EBPβ; LPS reduces Bach TF expression in progenitor cells and promotes myeloid differentiation; BACH1/BACH2 knockdown in human CD34+ HSPCs impairs erythroid differentiation in vitro. Bach2/Bach1 overexpression in HSPCs, BACH1/2 siRNA knockdown in human CD34+ cells, ChIP (binding to C/EBPβ regulatory regions), single-cell analysis, mouse infection models Nature immunology Medium 30250186
2020 The anti-angiogenic activity of BACH1 is mediated by its BTB domain: residues 81–89 of the BTB domain mediate direct binding to the N-terminal domain of TCF4, and the full-length HDAC1 (but not its interaction-domain mutant) co-precipitates with BACH1; the Bach1-ΔBTB mutant lacks these interactions and fails to suppress angiogenesis in vivo. Domain-deletion mutant (Bach1-ΔBTB) in adenovirus, Co-immunoprecipitation, hindlimb ischemia mouse model, capillary density and blood flow measurements EBioMedicine Medium 31911270
2023 BACH1 reduces lactate production by transcriptionally inhibiting HK2 and GAPDH during glycolysis in microglia; microglial BACH1 loss increases lactate-dependent histone modification (via histone lactylation) at the Lrrc15 promoter, and microglia-derived LRRC15 interacts with CD248 to activate JAK/STAT signaling and influence astrogenesis. Bach1 conditional KO mice (Cx3cr1-Cre), ChIP for histone lactylation at Lrrc15 promoter, Co-immunoprecipitation (LRRC15-CD248), glycolysis/lactate assays, behavioral testing Developmental cell Medium 38101413
2023 BACH1 transcriptionally activates KDM4C (a histone demethylase) by binding its promoter; KDM4C in turn occupies the COX2 promoter and promotes COX2 expression by removing H3K9me3, thereby driving ferroptosis in neuronal cells during cerebral ischemia-reperfusion injury. ChIP (BACH1 at KDM4C promoter; KDM4C at COX2 promoter), BACH1 knockdown, KDM4C and COX2 overexpression rescue, MCAO mouse model, ferroptosis markers The European journal of neuroscience Medium 37161649
2023 BACH1 directly interacts with the AT1R gene promoter in response to Ang II stimulation, increasing AT1R expression and activating Ca2+/CaMKII signaling to drive pathological cardiac hypertrophy; cardiac-specific BACH1 KO protects against Ang II- and TAC-induced hypertrophy, while cardiac BACH1 overexpression exacerbates it, with the AT1R antagonist losartan blunting BACH1-mediated CaMKII activation. Cardiac-specific BACH1 KO and transgenic mice, ChIP (BACH1 at AT1R promoter), Ang II and TAC hypertrophy models, CaMKII phosphorylation assays, Ca2+ measurements, losartan rescue Cardiovascular research High 37279500
2019 BACH1 recruits HMGA2 to promote EMT gene expression (Slug, Snail) in ovarian cancer cells and activates AKT/p70S6K signaling and cyclin D1 expression to drive proliferation and metastasis. BACH1 overexpression and knockout in A2780 cells, mouse metastasis model, Co-immunoprecipitation (BACH1-HMGA2), gene expression analysis Cancer letters Medium 30654010
2016 BACH1 antagonizes p53 function by competitively binding p53, preventing p53 from sequestering SP1; released SP1 then binds the MGMT promoter and increases MGMT expression, conferring temozolomide resistance in glioblastoma cells with wild-type TP53. BACH1 overexpression and knockdown in GBM cells, Co-immunoprecipitation (BACH1-p53), SP1-MGMT promoter binding assays, in vitro and in vivo TMZ resistance assays Scientific reports Medium 28000777
2022 ELK1 binds the BACH1 promoter (at a specific binding site) to activate BACH1 transcription; SETD8 interacts directly with ELK1 (shown by Co-IP and GST pull-down) and cooperates with BACH1 to regulate Snail transcription through H4K20 monomethylation, mediating EndMT in diabetic nephropathy. Co-IP and GST pull-down (SETD8-ELK1 interaction), ChIP (ELK1 and H4K20me1 at BACH1 promoter; SETD8/BACH1 at Snail promoter), dual-luciferase reporter assay, in vivo AAV-SETD8 injection Journal of translational medicine Medium 35351142
2024 Upon administration of the ketogenic diet, ATF4 levels are induced and ATF4 directly interacts with BACH1 to be recruited to pro-metastatic target promoters (including CEMIP encoding KIAA1549), enhancing BACH1-mediated transcriptional activation; genetic knockout or pharmacological inhibition of BACH1 abolishes keto diet-induced target activation and tumor metastasis. Co-immunoprecipitation (ATF4-BACH1), ChIP (BACH1 and ATF4 at target promoters), BACH1 KO and pharmacological inhibition in mouse cancer models, luciferase assays Science advances Medium 38838145
2023 BACH1 represses the biosynthesis of monounsaturated fatty acids by suppressing SCD1 expression, inducing ferroptosis; oleic acid (OA), a product of SCD1, rescues ferroptotic phenotypes of BACH1-overexpressing cells and reverses pro-metastatic properties, defining a BACH1→SCD1→OA axis that drives lymphatic metastasis. BACH1 overexpression in ESCC cells, transcriptomic and lipidomic analyses, OA supplementation rescue, mouse lymphatic metastasis models Cell death & disease Medium 36670112
2021 BACH1 directly binds the CD44 promoter (confirmed by ChIP-qPCR and dual-luciferase assay) to transcriptionally activate CD44, thereby inducing lung cancer stem cell properties; BACH1 effects on stem cells are mediated through the MAPK signaling pathway (p-p38, p-AKT1, c-Fos, c-Jun). ChIP-qPCR, dual-luciferase reporter assay, BACH1 shRNA knockdown, xenograft models, MAPK inhibitor experiments Respiratory research Medium 34949193
2023 FBXO22 promotes degradation of BACH1 in MLL-rearranged AML; FBXO22 deletion delays MLL-AF9-induced leukemogenesis and reduces leukemia stem cells, effects that are partially reversed by heterozygous BACH1 deletion, establishing BACH1 as a tumor suppressor downstream of FBXO22 in this context. Hematopoietic cell-specific Fbxo22 KO mice, MLL-AF9 AML model, immunoprecipitation/mass spectrometry (FBXO22 substrates), Western blot, serial transplantation assays, BACH1 heterozygous rescue Journal of hematology & oncology High 36774506
2018 MicroRNA-532-5p binds the BACH1 3' UTR (confirmed by luciferase assay), reducing BACH1 expression in pericytes; BACH1 silencing modulates angiopoietin-1 expression, and ChIP confirmed BACH1 transcriptional regulation of the angiopoietin-1 promoter, linking BACH1 to angiopoietin-1/Tie-2 signaling in vascular maturation. Luciferase reporter assay (miR-532-5p binding to BACH1 3'UTR), siRNA knockdown of BACH1, ChIP (BACH1 at angiopoietin-1 promoter), in vivo Matrigel assay Molecular therapy Medium 30274787
2023 BACH1 is required for USP14-mediated stabilization of BACH1 in ovarian cancer: activated NRF2 increases USP14 expression, and USP14 deubiquitinates and stabilizes BACH1 to suppress HMOX1 and promote OV cell invasion; BACH1 depletion significantly impairs USP14-dependent invasion. Proteomic identification of USP14 substrates, Co-immunoprecipitation, USP14 overexpression/knockdown, BACH1 knockdown, invasion assays Biochemical and biophysical research communications Medium 37229827
2024 BACH1 activates Fgf21 transcription and suppresses autophagic degradation of FGF21 through transcriptional repression of Sqstm1 and Lamp2 during ferroptosis; ferroptotic FGF21 secretion induced by BACH1 suppresses obesity in high-fat diet mice and extends lifespan in progeria mice. BACH1 re-expression in Bach1-/- iMEFs, Fgf21 knockout rescue, ChIP (BACH1 at Fgf21 promoter), conditioned medium transfer assays, in vivo mouse models (HFD obesity, progeria) Cell reports Medium 38943639
2021 BACH1 has a dual effect on CFTR expression: it directly occupies CFTR cis-regulatory elements at physiological oxygen (~8%) and can either activate or repress CFTR, and depletion of BACH1 alters higher-order chromatin structure at the CFTR locus (assessed by 4C-seq), indicating a role in locus architecture. siRNA knockdown screen, ChIP (BACH1 at CFTR CREs), 4C-seq (chromatin architecture), oxidative stress perturbations The Biochemical journal Medium 34605540
2023 BACH1 represses multiple antioxidant genes (including glutathione synthesis and iron metabolism genes), and Bach1 deletion in Mtb-infected mice increases glutathione levels and Gpx4 expression, reducing lipid peroxidation, ferroptosis, and necrosis; Bach1-/- macrophages show increased resistance to Mtb-induced cell death. Bach1 KO mice, Mtb infection models (including B6.Sst1S necrosis model), glutathione measurements, Gpx4 expression analysis, scRNA-seq of infected lungs, bacterial load quantification Nature microbiology High 38066332
2023 BACH1 transcriptionally activates a broad range of angiogenesis genes in lung cancer cells; BACH1 is a transcriptional target of HIF1α under hypoxia (BACH1 protein levels increase upon hypoxia and prolyl hydroxylase inhibition), but BACH1's pro-angiogenic transcriptional activity is HIF1α-independent. BACH1 overexpression and KO in lung cancer cells and xenografts, antioxidant treatment (vitamins C and E, NAC), tumor organoids, HIF1A KO cells, tumor vascularity in vivo, ChIP-seq/RNA-seq The Journal of clinical investigation High 37651203

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene. The EMBO journal 570 12356737
2019 BACH1 Stabilization by Antioxidants Stimulates Lung Cancer Metastasis. Cell 479 31257027
2019 Nrf2 Activation Promotes Lung Cancer Metastasis by Inhibiting the Degradation of Bach1. Cell 464 31257023
2019 Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism. Nature 276 30842661
2006 The heme-Bach1 pathway in the regulation of oxidative stress response and erythroid differentiation. Antioxidants & redox signaling 209 16487043
2004 The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations. Proceedings of the National Academy of Sciences of the United States of America 197 14983014
2022 Deletion of BACH1 Attenuates Atherosclerosis by Reducing Endothelial Inflammation. Circulation research 156 35196865
2006 Role of Bach1 and Nrf2 in up-regulation of the heme oxygenase-1 gene by cobalt protoporphyrin. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 139 17065227
2018 Bach1: Function, Regulation, and Involvement in Disease. Oxidative medicine and cellular longevity 138 30370001
2010 BACH1/FANCJ acts with TopBP1 and participates early in DNA replication checkpoint control. Molecular cell 132 20159562
2022 Ferroptosis: regulation by competition between NRF2 and BACH1 and propagation of the death signal. The FEBS journal 130 35107212
2019 Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1. Redox biology 130 31518892
2015 Bach1 Represses Wnt/β-Catenin Signaling and Angiogenesis. Circulation research 122 26123998
2007 Bach1, a heme-dependent transcription factor, reveals presence of multiple heme binding sites with distinct coordination structure. IUBMB life 100 17701549
2020 BACH1 Promotes Pancreatic Cancer Metastasis by Repressing Epithelial Genes and Enhancing Epithelial-Mesenchymal Transition. Cancer research 97 31919242
2011 Hereditary breast cancer and the BRCA1-associated FANCJ/BACH1/BRIP1. Future oncology (London, England) 92 21345144
2016 BACH1, the master regulator gene: A novel candidate target for cancer therapy. Gene 90 27108804
2021 A Novel Therapeutic Target, BACH1, Regulates Cancer Metabolism. Cells 79 33809182
2021 The transcription factor BACH1 at the crossroads of cancer biology: From epithelial-mesenchymal transition to ferroptosis. The Journal of biological chemistry 75 34339740
2022 UBR7 inhibits HCC tumorigenesis by targeting Keap1/Nrf2/Bach1/HK2 and glycolysis. Journal of experimental & clinical cancer research : CR 72 36419136
2006 BACH1 is a DNA repair protein supporting BRCA1 damage response. Oncogene 70 16462773
2010 Expression of heme oxygenase-1 in human leukemic cells and its regulation by transcriptional repressor Bach1. Cancer science 67 20345481
2019 BTB and CNC homology 1 (Bach1) promotes human ovarian cancer cell metastasis by HMGA2-mediated epithelial-mesenchymal transition. Cancer letters 63 30654010
2008 BACH1 is a specific repressor of HMOX1 that is inactivated by arsenite. The Journal of biological chemistry 62 18550526
2016 Bach1 Induces Endothelial Cell Apoptosis and Cell-Cycle Arrest through ROS Generation. Oxidative medicine and cellular longevity 60 27057283
2019 Bach1 regulates self-renewal and impedes mesendodermal differentiation of human embryonic stem cells. Science advances 58 30891497
2022 Interplay of Nrf2 and BACH1 in inducing ferroportin expression and enhancing resistance of human macrophages towards ferroptosis. Cell death discovery 56 35853860
2023 BACH1 changes microglial metabolism and affects astrogenesis during mouse brain development. Developmental cell 47 38101413
2023 BACH1 promotes tissue necrosis and Mycobacterium tuberculosis susceptibility. Nature microbiology 46 38066332
2023 BACH1-induced ferroptosis drives lymphatic metastasis by repressing the biosynthesis of monounsaturated fatty acids. Cell death & disease 44 36670112
2021 Chronic intermittent hypoxia promoted lung cancer stem cell-like properties via enhancing Bach1 expression. Respiratory research 43 33596919
2023 Antioxidants stimulate BACH1-dependent tumor angiogenesis. The Journal of clinical investigation 41 37651203
2019 TLR4 activation alters labile heme levels to regulate BACH1 and heme oxygenase-1 expression in macrophages. Free radical biology & medicine 41 31026585
2013 Bach1 deficiency protects pancreatic β-cells from oxidative stress injury. American journal of physiology. Endocrinology and metabolism 41 23880309
2005 Mutation analysis of FANCD2, BRIP1/BACH1, LMO4 and SFN in familial breast cancer. Breast cancer research : BCR 41 16280053
2021 BACH1 recruits NANOG and histone H3 lysine 4 methyltransferase MLL/SET1 complexes to regulate enhancer-promoter activity and maintains pluripotency. Nucleic acids research 39 33503260
2022 Overexpression of BACH1 mediated by IGF2 facilitates hepatocellular carcinoma growth and metastasis via IGF1R and PTK2. Theranostics 38 35154476
2020 The BACH1/Nrf2 Axis in Brain in Down Syndrome and Transition to Alzheimer Disease-Like Neuropathology and Dementia. Antioxidants (Basel, Switzerland) 38 32839417
2019 HMGA2 and Bach-1 cooperate to promote breast cancer cell malignancy. Journal of cellular physiology 38 30825204
2018 BACH1 promotes the progression of human colorectal cancer through BACH1/CXCR4 pathway. Biochemical and biophysical research communications 38 29481800
2004 Transgenic expression of BACH1 transcription factor results in megakaryocytic impairment. Blood 38 15613547
2006 Assessing the link between BACH1 and BRCA1 in the FA pathway. Cell cycle (Georgetown, Tex.) 36 16357529
2023 BACH1 controls hepatic insulin signaling and glucose homeostasis in mice. Nature communications 35 38129407
2016 BACH1 Promotes Temozolomide Resistance in Glioblastoma through Antagonizing the Function of p53. Scientific reports 35 28000777
2023 BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility. Nucleic acids research 34 36864760
2022 Harnessing the Therapeutic Potential of the Nrf2/Bach1 Signaling Pathway in Parkinson's Disease. Antioxidants (Basel, Switzerland) 33 36139853
2020 Isomeric O-methyl cannabidiolquinones with dual BACH1/NRF2 activity. Redox biology 33 32863231
2018 Infection perturbs Bach2- and Bach1-dependent erythroid lineage 'choice' to cause anemia. Nature immunology 33 30250186
2021 Challenges and Limitations of Targeting the Keap1-Nrf2 Pathway for Neurotherapeutics: Bach1 De-Repression to the Rescue. Frontiers in aging neuroscience 32 33897412
2017 Differentiation impairs Bach1 dependent HO-1 activation and increases sensitivity to oxidative stress in SH-SY5Y neuroblastoma cells. Scientific reports 32 28790431
2020 Bach1-induced suppression of angiogenesis is dependent on the BTB domain. EBioMedicine 31 31911270
2024 Sanguinarine chloride induces ferroptosis by regulating ROS/BACH1/HMOX1 signaling pathway in prostate cancer. Chinese medicine 30 38195593
2024 Transcription factor BACH1 in cancer: roles, mechanisms, and prospects for targeted therapy. Biomarker research 30 38321558
2020 Omega-3 fatty acids protect against acetaminophen-induced hepatic and renal toxicity in rats through HO-1-Nrf2-BACH1 pathway. Archives of biochemistry and biophysics 30 32348741
2018 MicroRNA-532-5p Regulates Pericyte Function by Targeting the Transcription Regulator BACH1 and Angiopoietin-1. Molecular therapy : the journal of the American Society of Gene Therapy 29 30274787
2020 Downregulation of BACH1 Protects AGAINST Cerebral Ischemia/Reperfusion Injury through the Functions of HO-1 and NQO1. Neuroscience 28 32311410
2019 Silencing Bach1 alters aging-related changes in the expression of Nrf2-regulated genes in primary human bronchial epithelial cells. Archives of biochemistry and biophysics 28 31422075
2024 Recognition of BACH1 quaternary structure degrons by two F-box proteins under oxidative stress. Cell 27 39504958
2021 BTB and CNC homology 1 (Bach1) induces lung cancer stem cell phenotypes by stimulating CD44 expression. Respiratory research 27 34949193
2023 Cardiac-specific BACH1 ablation attenuates pathological cardiac hypertrophy by inhibiting the Ang II type 1 receptor expression and the Ca2+/CaMKII pathway. Cardiovascular research 26 37279500
2020 LncRNA MIR17HG inhibits non-small cell lung cancer by upregulating miR-142-3p to downregulate Bach-1. BMC pulmonary medicine 26 32228546
2022 The SETD8/ELK1/bach1 complex regulates hyperglycaemia-mediated EndMT in diabetic nephropathy. Journal of translational medicine 25 35351142
2022 BACH1-Hemoxygenase-1 axis regulates cellular energetics and survival following sepsis. Free radical biology & medicine 24 35691510
2022 The dual role and mutual dependence of heme/HO-1/Bach1 axis in the carcinogenic and anti-carcinogenic intersection. Journal of cancer research and clinical oncology 24 36310300
2021 BACH1 promotes the progression of esophageal squamous cell carcinoma by inducing the epithelial-mesenchymal transition and angiogenesis. Cancer medicine 24 33932125
2014 Bach1 deficiency and accompanying overexpression of heme oxygenase-1 do not influence aging or tumorigenesis in mice. Oxidative medicine and cellular longevity 24 25050144
2009 Bach1 modulates heme oxygenase-1 expression in the neonatal mouse lung. Pediatric research 24 18948842
2024 An unexpected role for the ketogenic diet in triggering tumor metastasis by modulating BACH1-mediated transcription. Science advances 23 38838145
2022 Inhibiting BTB domain and CNC homolog 1 (Bach1) as an alternative to increase Nrf2 activation in chronic diseases. Biochimica et biophysica acta. General subjects 23 35292311
2019 Does Bach1 & c-Myc dependent redox dysregulation of Nrf2 & adaptive homeostasis decrease cancer risk in ageing? Free radical biology & medicine 23 30695691
2014 Cell-type-specific downregulation of heme oxygenase-1 by lipopolysaccharide via Bach1 in primary human mononuclear cells. Free radical biology & medicine 23 25463280
2010 Bach1-dependent and -independent regulation of heme oxygenase-1 in keratinocytes. The Journal of biological chemistry 23 20501657
2010 Assessing the link between BACH1/FANCJ and MLH1 in DNA crosslink repair. Environmental and molecular mutagenesis 23 20658644
2023 FBXO22 promotes leukemogenesis by targeting BACH1 in MLL-rearranged acute myeloid leukemia. Journal of hematology & oncology 22 36774506
2023 BACH1 encourages ferroptosis by activating KDM4C-mediated COX2 demethylation after cerebral ischemia-reperfusion injury. The European journal of neuroscience 22 37161649
2021 BACH1, the master regulator of oxidative stress, has a dual effect on CFTR expression. The Biochemical journal 22 34605540
2019 BACH1 mediates the antioxidant properties of aged garlic extract. Experimental and therapeutic medicine 22 32010329
2023 Deletion of BACH1 alleviates ferroptosis and protects against LPS-triggered acute lung injury by activating Nrf2/HO-1 signaling pathway. Biochemical and biophysical research communications 21 36621150
2021 MiR-133a-3p relieves the oxidative stress induced trophoblast cell apoptosis through the BACH1/Nrf2/HO-1 signaling pathway. Physiological research 21 33453713
2021 LncRNA SNHG5 promotes the glycolysis and proliferation of breast cancer cell through regulating BACH1 via targeting miR-299. Breast cancer (Tokyo, Japan) 21 34351577
2020 Circular RNA circ_0000337 contributes to osteosarcoma via the miR-4458/BACH1 pathway. Cancer biomarkers : section A of Disease markers 21 32390598
2023 Ferroptosis model system by the re-expression of BACH1. Journal of biochemistry 20 37094356
2021 BACH1 as a potential target for immunotherapy in glioblastomas. International immunopharmacology 19 34923423
2023 The BACH1 inhibitor ASP8731 inhibits inflammation and vaso-occlusion and induces fetal hemoglobin in sickle cell disease. Frontiers in medicine 18 37144034
2024 An iron-rich subset of macrophages promotes tumor growth through a Bach1-Ednrb axis. The Journal of experimental medicine 17 39347789
2022 CAPE and its synthetic derivative VP961 restore BACH1/NRF2 axis in Down Syndrome. Free radical biology & medicine 17 35283228
2020 Bach1 promotes muscle regeneration through repressing Smad-mediated inhibition of myoblast differentiation. PloS one 17 32776961
2018 Aberration of Nrf2‑Bach1 pathway in colorectal carcinoma; role in carcinogenesis and tumor progression. Annals of diagnostic pathology 17 30597358
2006 New biotechnological methods to reduce oxidative stress in the cardiovascular system: focusing on the Bach1/heme oxygenase-1 pathway. Current pharmaceutical biotechnology 17 16724942
2021 Comprehensive Mutational Analysis of the BRCA1-Associated DNA Helicase and Tumor-Suppressor FANCJ/BACH1/BRIP1. Molecular cancer research : MCR 16 33619228
2019 S-1-Propenylcysteine augments BACH1 degradation and heme oxygenase 1 expression in a nitric oxide-dependent manner in endothelial cells. Nitric oxide : biology and chemistry 16 30630055
2025 The Multifaceted Roles of BACH1 in Disease: Implications for Biological Functions and Therapeutic Applications. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 15 39887888
2023 Tert-butyl hydroperoxide induces ferroptosis of bone mesenchymal stem cells by repressing the prominin2/BACH1/ROS axis. American journal of physiology. Cell physiology 15 37721001
2023 Lnc AC016727.1/BACH1/HIF-1 α signal loop promotes the progression of non-small cell lung cancer. Journal of experimental & clinical cancer research : CR 15 37946265
2024 BACH1 inhibits senescence, obesity, and short lifespan by ferroptotic FGF21 secretion. Cell reports 14 38943639
2023 USP14 regulates heme metabolism and ovarian cancer invasion through BACH1 deubiquitination and stabilization. Biochemical and biophysical research communications 14 37229827
2022 Enhancing the HSV-1-mediated antitumor immune response by suppressing Bach1. Cellular & molecular immunology 14 34983952
2022 BACH1 promotes clear cell renal cell carcinoma progression by upregulating oxidative stress-related tumorigenicity. Cancer science 14 36178067
2022 Ryanodine receptor 2 promotes colorectal cancer metastasis by the ROS/BACH1 axis. Molecular oncology 14 36453019
2020 Defective BACH1/HO-1 regulatory circuits in cystic fibrosis bronchial epithelial cells. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 14 32534959

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