Affinage

BHLHE40

Class E basic helix-loop-helix protein 40 · UniProt O14503

Length
412 aa
Mass
45.5 kDa
Annotated
2026-04-28
100 papers in source corpus 54 papers cited in narrative 54 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BHLHE40 is a basic helix-loop-helix transcriptional repressor—and context-dependent activator—that integrates circadian, hypoxic, and immune signals to control gene expression programs governing cell proliferation, differentiation, and inflammatory responses. It represses target genes primarily by competing with CLOCK:BMAL1 and other bHLH/bHLHZip factors (USF, ChREBP, SREBP-1c, SP1) for E-box binding and by recruiting HDAC1/2 to promoters, with SUMOylation at K159/K279 stabilizing the protein and potentiating HDAC1-dependent repression (PMID:9284045, PMID:21829689, PMID:22905217, PMID:14581485, PMID:18838394). In immune cells, BHLHE40 is required cell-intrinsically for GM-CSF and IFN-γ production, IL-10 suppression, macrophage self-renewal, germinal center restraint, and CD8+ T cell exhaustion checkpoint control; its loss renders T cells nonencephalitogenic and impairs anti-tumor immunity and checkpoint-blockade responses (PMID:24699451, PMID:29773643, PMID:31061528, PMID:31533057, PMID:37595022). BHLHE40 protein stability is governed by SCFβTrCP/CK1-mediated ubiquitination driving degradation and USP17-mediated deubiquitination stabilizing it after DNA damage, while interactions with p53, STAT3, T-bet, Runx1, and PGC-1α direct its activity toward specific gene programs including apoptosis, cytokine regulation, and mitochondrial/metabolic control (PMID:25202122, PMID:17347673, PMID:15223310, PMID:27226296, PMID:25963661).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1997 High

    Establishing that BHLHE40 is a bHLH transcriptional repressor that acts through its α-helix-rich C-terminal domain rather than through canonical E-box binding defined the gene's foundational molecular identity.

    Evidence Transient transfection reporter assays and protein-protein interaction studies in P19 cells

    PMID:9284045

    Open questions at the time
    • No endogenous target genes identified
    • Mechanism of repression (direct vs. cofactor-mediated) unresolved
    • In vivo relevance not tested
  2. 2001 High

    Demonstrating that BHLHE40 physically antagonizes USF via its C-terminal domain and that Bhlhe40-knockout mice develop autoimmunity with lymphocyte accumulation revealed both a bHLH-factor competition mechanism and an essential in vivo role in immune homeostasis.

    Evidence Yeast two-hybrid, co-immunoprecipitation, and reporter assays for USF interaction; Stra13-KO mouse model with lymphocyte phenotyping

    PMID:11498797 PMID:11668339

    Open questions at the time
    • Direct transcriptional targets in T cells unknown
    • Whether immune phenotype reflects repressor or activator function unclear
    • Redundancy with BHLHE41 not addressed
  3. 2002 High

    Identification of HIF-1α/β binding to the BHLHE40 promoter HRE placed BHLHE40 as a direct hypoxia-responsive gene, establishing its role as a transcriptional effector linking oxygen sensing to downstream gene regulation.

    Evidence Luciferase reporters, EMSA with HIF-1α/β, deletion/mutation analysis of HRE

    PMID:12354771

    Open questions at the time
    • Hypoxia-regulated target genes of BHLHE40 not yet catalogued
    • Relationship between hypoxia and circadian functions not integrated
  4. 2003 High

    Showing that CLOCK:BMAL1 drives circadian BHLHE40 expression and that BHLHE40 represses its own promoter via E-box binding established BHLHE40 as an autoregulatory component of the peripheral circadian clock.

    Evidence Reporter assays and microarray in Stra13−/− mouse liver; DEC1-DEC2 cross-repression via E-box mutagenesis

    PMID:12624110 PMID:14581485

    Open questions at the time
    • Whether BHLHE40 is essential for core clock function or only modulatory
    • Redundancy with DEC2/CRY in clock repression not resolved
  5. 2004 High

    Dissecting that BHLHE40 represses mPer1 through direct E-box DNA binding rather than through protein-protein interaction with BMAL1 resolved the primary repression mechanism in the clock circuit, while identification of STAT3 interaction revealed a non-E-box co-regulatory mode.

    Evidence DNA-binding mutant analysis for mPer1 repression; yeast two-hybrid and co-IP for STAT3 interaction with functional reporter assays

    PMID:15193144 PMID:15223310

    Open questions at the time
    • Genome-wide binding profile not available
    • STAT3 interaction not validated in vivo
    • Whether E-box-dependent and STAT3-dependent functions operate in the same cell types unclear
  6. 2006 High

    Demonstrating that BHLHE40 recruits HDAC1 via its C-terminal domain to repress STAT1 and that it activates the survivin promoter through Sp1 sites established HDAC-dependent repression and context-dependent activation as dual modes of action.

    Evidence ChIP, TSA inhibition, Sp1-site mutagenesis, and EMSA at survivin and STAT1 promoters

    PMID:16462771 PMID:16878149

    Open questions at the time
    • Full HDAC family involvement not mapped
    • Structural basis for context-dependent activation vs. repression unknown
  7. 2007 High

    Discovery that BHLHE40 stabilizes p53 by blocking Mdm2-mediated ubiquitination and that p53 reciprocally induces BHLHE40 transcription defined a positive-feedback circuit coupling DNA damage to apoptosis and senescence; separately, BHLHE40 was shown to antagonize Notch signaling in satellite cells and to promote TGF-β-dependent metastatic survival.

    Evidence Stra13−/− thymocytes with reduced p53/Puma/Noxa after irradiation; in vitro ubiquitination assays; Notch rescue in KO myoblasts; dominant-negative DEC1 in metastasis model

    PMID:17347673 PMID:17502421 PMID:17942899 PMID:18025081

    Open questions at the time
    • Direct p53-binding domain on BHLHE40 not mapped
    • Whether Notch antagonism is direct or transcriptional unclear
    • TGF-β survival mechanism not fully defined
  8. 2008 High

    A series of studies identified endogenous BHLHE40 target promoters (BDNF exon 4, MLH1, SREBP-1c, ChREBP targets, ATP1B1) repressed through E-box binding and HDAC-dependent mechanisms, and showed TGF-β/SMAD3-dependent induction of BHLHE40 mediates non-photic circadian clock resetting in vivo.

    Evidence EMSA/ChIP in hippocampal neurons and hepatocytes; Bhlhe40−/− mice for BDNF and clock resetting; TSA rescue for MLH1; Dec1−/− mice with TGF-β injection

    PMID:18234890 PMID:18345027 PMID:18602890 PMID:18838394 PMID:19029909

    Open questions at the time
    • Genome-wide target repertoire still lacking
    • Tissue-specific vs. universal targets not distinguished
  9. 2011 High

    Identification of SUMOylation at K159/K279 as a stabilizing modification that promotes nuclear retention, HDAC1 recruitment, and enhanced CLOCK:BMAL1 repression provided the first post-translational regulatory code for BHLHE40 activity.

    Evidence SUMO modification assays, site-directed mutagenesis, ubiquitination assays, reporter assays in COS-7/MCF-7 cells

    PMID:21829689 PMID:22905217

    Open questions at the time
    • SUMO E3 ligase responsible not identified
    • In vivo relevance of SUMOylation not tested
    • Interplay between SUMOylation and ubiquitination pathways not resolved
  10. 2014 High

    Defining BHLHE40 as a cell-intrinsic regulator of GM-CSF and IL-10 in T cells, identifying the SCFβTrCP/CK1-dependent degradation and USP17-dependent stabilization axis, and showing BHLHE40 co-activates IFN-γ with T-bet at the Ifng locus established its immune effector function and protein turnover control.

    Evidence Bhlhe40−/− EAE model with IL-10R blockade rescue; Co-IP of SCFβTrCP and USP17 with ubiquitination assays; ChIP at Ifng locus with histone acetylation analysis

    PMID:24699451 PMID:25202122 PMID:27226296

    Open questions at the time
    • Whether T-bet-dependent and -independent IFN-γ regulation co-occur in same T cell subsets
    • CK1 phosphorylation sites on BHLHE40 not fully mapped
    • USP17 regulation in immune cells unknown
  11. 2015 High

    Showing that BHLHE40 directly binds and represses PGC-1α transactivation by recruiting HDACs and preventing relief of PGC-1α intramolecular repression established BHLHE40 as a metabolic corepressor controlling mitochondrial gene programs.

    Evidence Co-immunoprecipitation of Bhlhe40-PGC-1α, ChIP at target promoters, HDAC recruitment assays, siRNA knockdown

    PMID:25963661

    Open questions at the time
    • In vivo metabolic phenotype of Bhlhe40 KO not fully characterized
    • Peroxisome vs. mitochondria specificity mechanism unclear
  12. 2019 High

    Genome-wide binding studies and functional genetics revealed BHLHE40 sustains mitochondrial fitness and epigenetic openness in tissue-resident memory and tumor-infiltrating CD8+ T cells, controls macrophage self-renewal by repressing Maf family genes, and maintains alveolar macrophage identity—establishing BHLHE40 as a master regulator of immune cell fitness and identity.

    Evidence ChIP-seq in peritoneal and alveolar macrophages; ATAC-seq in TILs; conditional KO with anti-PD-L1 treatment; Bhlhe40/41 double-KO

    PMID:31061528 PMID:31414712 PMID:31533057

    Open questions at the time
    • Direct transcriptional targets mediating mitochondrial fitness in T cells not defined
    • Whether macrophage and T cell programs share common BHLHE40 target genes
    • BHLHE40 vs. BHLHE41 functional redundancy quantitatively unresolved
  13. 2022 Medium

    CRISPR screens and in vivo models placed BHLHE40 at the differentiation checkpoint between progenitor and intermediate exhausted CD8+ T cells and showed it is required for effective anti-PD-1/anti-CTLA-4 immunotherapy responses, linking its transcriptional program to clinical checkpoint blockade efficacy.

    Evidence Genome-wide CRISPR screen with chronic stimulation model; Bhlhe40−/− tumor models with ICT; scRNA-seq

    PMID:35181783 PMID:37595022

    Open questions at the time
    • Direct gene targets at the exhaustion checkpoint not mapped by ChIP
    • Human patient validation limited
    • Whether BHLHE40 is therapeutically targetable
  14. 2023 High

    Multi-omics approaches revealed that BHLHE40 physically mediates enhancer-promoter looping at the SREBF1 locus to regulate lipid desaturation and ferroptosis resistance, and represses MAFA via displacement of PDX1 to suppress insulin secretion in hypoxic β-cells, expanding its mechanistic repertoire to 3D genome organization and metabolic disease.

    Evidence ChIP-seq, Hi-C/chromosome conformation capture at SREBF1; ChIP at Mafa enhancer in MIN6 cells and ob/ob mice with rescue

    PMID:37341148 PMID:38064101

    Open questions at the time
    • Genome-wide enhancer-promoter bridging role not assessed beyond SREBF1
    • Structural basis for chromatin looping activity unknown
    • β-cell findings not validated in human islets
  15. 2024 High

    Demonstrating that BHLHE40/41 loss in macrophages de-represses disease-associated macrophage (DLAM) genes governing cholesterol efflux and lysosomal processing established BHLHE40 as a gatekeeper of macrophage activation states relevant to neurodegeneration and atherosclerosis.

    Evidence BHLHE40/41 KO in iPSC-derived microglia, THP-1, and mouse models; scRNA-seq gene regulatory network reconstruction; lipid/lysosomal functional assays

    PMID:38448474

    Open questions at the time
    • In vivo disease model validation (e.g., atherosclerosis, Alzheimer's) not performed
    • Whether therapeutic de-repression of DLAM is beneficial or detrimental long-term

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite extensive characterization, the structural basis for BHLHE40's dual repressor/activator activity, its genome-wide binding landscape across immune cell states, the full extent of BHLHE40-BHLHE41 functional redundancy, and whether BHLHE40 can be therapeutically modulated in cancer immunotherapy or metabolic disease remain unresolved.
  • No crystal or cryo-EM structure of BHLHE40 or its complexes
  • Systematic comparison of BHLHE40 vs. BHLHE41 ChIP-seq across cell types lacking
  • No pharmacological tool compounds reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 12 GO:0003677 DNA binding 11 GO:0098772 molecular function regulator activity 3 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 12 R-HSA-168256 Immune System 11 R-HSA-162582 Signal Transduction 5 R-HSA-8953897 Cellular responses to stimuli 5 R-HSA-1430728 Metabolism 4 R-HSA-1640170 Cell Cycle 4 R-HSA-9909396 Circadian clock 4 R-HSA-4839726 Chromatin organization 3 R-HSA-5357801 Programmed Cell Death 1
Partners
HDAC1HDAC2PGC1ARUNX1STAT3TBX21TP53USF1

Evidence

Reading pass · 54 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 BHLHE40 (Stra13) encodes a bHLH protein that represses activated transcription through an alpha-helix rich C-terminal domain, in part by interaction with general factors of the basal transcription machinery, and does not bind the canonical E-box or N-box motifs recognized by other bHLH proteins. Transient transfection reporter assays, protein-protein interaction studies, overexpression in P19 cells Genes & development High 9284045
2001 Stra13 (BHLHE40) interacts physically with the bHLHZip protein USF through its C-terminal repression domain and the DNA-binding domain of USF; co-expression causes mutual functional antagonism, with USF abrogating Stra13-mediated repression and Stra13 inhibiting USF DNA binding and transactivation. Yeast two-hybrid screen, co-immunoprecipitation, reporter assays, EMSA Oncogene High 11498797
2001 BHLHE40 (Stra13) is required for proper CD4+ T cell activation and elimination of activated lymphocytes; Stra13-deficient mice develop autoimmune disease with accumulation of activated T and B cells, indicating a key role in lymphocyte homeostasis. Stra13-knockout mouse model, in vivo lymphocyte phenotyping, immunology assays Nature immunology High 11668339
2002 HIF-1α and HIF-1β directly bind functional hypoxia response elements (HREs) in the BHLHE40 (DEC1) promoter region (-524 to -401), activating its transcription in response to hypoxia or CoCl2. Luciferase reporter assays, EMSA showing HIF-1α/β binding to HRE, deletion/mutation analysis The Journal of biological chemistry High 12354771
2002 DEC1 (BHLHE40) promotes chondrocyte differentiation when overexpressed in ATDC5 cells, antagonizes the inhibitory action of PTH/PTHrP, and induces expression of type II collagen, Indian hedgehog, and Runx2. Forced expression in ATDC5 cells and bone marrow mesenchymal stem cells, gene expression analysis The Journal of biological chemistry Medium 12384505
2003 DEC1 (BHLHE40) directly binds an E-box motif in the proximal promoter of DEC2 and represses DEC2 transcription; DNA-binding-defective DEC1 mutants lose this repressive activity. Reporter assays with deletion/site-directed mutants, stable transfectants with tetracycline-inducible DEC1 The Journal of biological chemistry High 12624110
2003 BHLHE40 (Stra13) circadian expression in peripheral tissues is driven by the CLOCK-BMAL1 heterodimer via a response element in the proximal promoter; Stra13 in turn represses its own CLOCK-BMAL1-driven transcription (autorepression), and CRY1 strongly represses CLOCK-BMAL1-dependent Stra13 activation. Reporter assays, microarray gene expression in Stra13-/- mice liver, genetic knockout The Journal of biological chemistry High 14581485
2004 DEC1 (BHLHE40) represses the mPer1 promoter through direct E-box binding rather than through protein-protein interaction with Bmal1; DNA-binding mutants of DEC1 that retain Bmal1 interaction cannot repress the mPer1 promoter. Reporter assays, yeast two-hybrid, EMSA, mutational analysis The Biochemical journal High 15193144
2004 STRA13 (BHLHE40) interacts with phosphorylated (active) STAT3α and STAT3β via its HLH and C-terminal regions; STRA13 can activate transcription from STAT-dependent elements and modulates the transcriptional outcome of STAT3 on the Fas promoter. Yeast two-hybrid, co-immunoprecipitation, luciferase reporter assays Journal of molecular biology High 15223310
2005 STRA13 (BHLHE40) interacts with MSP58 via its basic domain (with MSP58's FHA domain required), and complex formation protects both proteins from proteasome-mediated degradation; together they synergistically co-operate in STRA13 promoter-driven transcription repression. Yeast two-hybrid, Co-IP, phospho-peptide mapping, protein half-life assays, reporter assays Cellular and molecular life sciences Medium 15719173
2006 STRA13 (BHLHE40) represses STAT1 transcription through a mechanism requiring its C-terminal trans-activation domain which binds HDAC1; this HDAC-dependent mechanism also results in repression of STAT1 target genes (MHC antigen-presenting genes, CASP1) under hypoxia via VHL/HIF-1 activation. Luciferase reporter assays with deletion/site-directed mutants, ChIP, TSA inhibition Oncogene High 16878149
2006 DEC1 (BHLHE40) transactivates the survivin promoter through two Sp1 sites, and DEC1 protein is detected at the survivin promoter by EMSA and ChIP, establishing survivin as a direct transcriptional target. Reporter assays with Sp1 site mutants, EMSA, ChIP Oncogene High 16462771
2007 DEC1 (BHLHE40) is a direct transcriptional target of the p53 family; p53 family proteins bind and activate the DEC1 promoter, and DEC1 overexpression induces G1 arrest and premature senescence independently of p21. cDNA microarray, luciferase reporter assays, ChIP showing p53 binding to DEC1 promoter, siRNA knockdown The Journal of biological chemistry High 18025081
2007 Stra13 (BHLHE40) physically interacts with p53 in vitro and prevents Mdm2-mediated ubiquitination and nuclear export of p53, thereby stabilizing p53 levels to promote ionizing-radiation-induced apoptosis; Stra13-deficient thymocytes show reduced p53, Puma, and Noxa expression after irradiation. Stra13-/- mouse model, in vitro interaction assay, ubiquitination assay, gene expression EMBO reports High 17347673
2007 Stra13 (BHLHE40) modulates satellite cell activation by antagonizing Notch signaling; Stra13-/- primary myoblasts show enhanced Notch activity, increased proliferation, and defective differentiation, and inhibition of Notch signaling rescues the regeneration defect of Stra13-/- mice. Stra13 knockout mouse model, in vitro Notch pathway reporter assays, pharmacological Notch inhibition rescue The Journal of cell biology High 17502421
2007 DEC1 (BHLHE40) is induced by TGF-β signaling in mammary carcinoma cells and promotes cell survival; knockdown of DEC1 abrogates TGF-β-promoted cell survival, and a dominant-negative DEC1 mutant prevents lung and liver metastasis in vivo. Microarray, kinase inhibitor treatment, dominant-negative overexpression, in vivo metastasis model Cancer research High 17942899
2008 BHLHE40 (BHLHB2) binds a specific sequence within Bdnf promoter 4 and mediates transcriptional repression; NMDA receptor activation reduces BHLHB2 occupancy at promoter 4, correlating with de-repressed BDNF exon 4 expression; Bhlhb2-/- mice show increased hippocampal BDNF exon 4 mRNA. EMSA, ChIP in hippocampal neurons, Bhlhb2 knockout mice The Journal of neuroscience High 18234890
2008 TGF-β/activin signaling resets the circadian clock through SMAD3-dependent immediate-early induction of Dec1 (BHLHE40); intraperitoneal TGF-β injection in wild-type but not Dec1-deficient mice produces phase-shifts in peripheral clock gene expression, establishing Dec1 as an essential mediator of this non-light resetting pathway. ALK inhibitor/activator treatment, SMAD3 phosphorylation assays, Dec1-/- mouse model, in vivo clock gene expression Nature cell biology High 19029909
2008 DEC1/STRA13 and DEC2 repress SREBP-1c by competing with SREBP-1c for binding to the E-box in the SREBP-1c promoter and/or by protein-protein interaction with SREBP-1c; DEC2 initiates acute hypoxic repression while DEC1 substitutes during prolonged hypoxia. Reporter assays, siRNA knockdown, protein-protein interaction assays Nucleic acids research High 18838394
2008 DEC1 (BHLHB2) and DEC2 transcriptionally repress MLH1 by directly binding E-box-like motifs in the MLH1 promoter; repression is abolished by the HDAC inhibitor trichostatin A, indicating a histone deacetylase-dependent mechanism. Reporter assays, site-directed mutagenesis, EMSA, ChIP, TSA inhibition Oncogene High 18345027
2008 BHLHB2/DEC1 (BHLHE40) suppresses ChREBP-mediated lipogenic gene expression by binding to carbohydrate response elements (ChoRE) in the Fasn, Lpk, and Bhlhb2 promoters, forming a negative feedback loop with ChREBP. ChIP in rat hepatocytes, reporter deletion assays, overexpression studies Biochemical and biophysical research communications Medium 18602890
2009 Bhlhe40 binds to adjacent E-boxes (E1-box) on the PGC-1α core promoter and represses MyoD-mediated transactivation by sequestering the co-activator P/CAF from MyoD; P/CAF can relieve Bhlhe40-mediated repression in a dose-dependent manner. EMSA, ChIP, co-immunoprecipitation, reporter assays The Biochemical journal High 19522704
2010 Dec1 (BHLHE40) interacts physically with the transcription factor Runx1 in regulatory T cells; the Dec1/Runx1 complex binds regulatory elements of the Il-2rα (CD25) locus, upregulating CD25 expression and supporting Treg homeostasis. Co-immunoprecipitation, ChIP at Il-2rα locus, enforced Dec1 expression in thymocytes Journal of immunology High 21057086
2011 DEC1 (BHLHE40) directly binds a DEC-response element in the cyclin D1 promoter and represses cyclin D1 expression, linking DEC1 to G1/S cell cycle control. Reporter assays with cyclin D1 promoter mutants, ChIP confirming direct binding The Journal of pathology High 21506129
2011 DEC1 (BHLHE40) physically interacts with HDAC2 and increases binding of DEC1 to the ΔNp63 promoter when HDAC2 is knocked down; DEC1 represses ΔNp63 expression and thereby modulates keratinocyte differentiation. Co-immunoprecipitation, ChIP, siRNA knockdown, reporter assays The Journal of biological chemistry High 21317427
2011 SUMOylation of DEC1 (BHLHE40) at K159 and K279 stabilizes the protein by inhibiting ubiquitination, promotes its nuclear retention, and potentiates repression of CLOCK/BMAL1-mediated transcriptional activity through recruitment of HDAC1. SUMO modification assay in COS-7/MCF-7 cells, site-directed mutagenesis of SUMO acceptor lysines, ubiquitination assay, reporter assays PloS one High 21829689
2012 SUMOylation of Stra13 (BHLHE40) at K159 and K279 potentiates transcriptional repression of cyclin D1 and G1 cell cycle arrest by enabling association with the co-repressor HDAC1; SUMO-site mutants localize normally to the nucleus but lose HDAC1 interaction and growth-suppressive activity. SUMO-site mutagenesis, co-immunoprecipitation with HDAC1, reporter assays, cell cycle analysis PloS one High 22905217
2012 DEC1 (BHLHE40) represses PPARγ2 transcription by physically interacting with C/EBPβ already bound to the PPARγ2 promoter; DEC1 occupancy is accompanied by increased HDAC1 recruitment and reduced histone acetylation at the promoter. Co-immunoprecipitation, ChIP, reporter assays, adipogenic differentiation assay Molecules and cells High 22610404
2014 Bhlhe40 (BHLHE40) is required cell-intrinsically in T cells to positively regulate GM-CSF production and negatively regulate IL-10 production; Bhlhe40-deficient mice are resistant to EAE and IL-10 receptor blockade restores susceptibility. Bhlhe40-/- mouse model, T cell adoptive transfer, cytokine ELISA, IL-10R blockade rescue Nature communications High 24699451
2014 DEC1 (BHLHE40) coordinates with HDAC8 to differentially regulate TAp73 and ΔNp73: DEC1 activates TAp73 by recruiting HDAC8 to the TAp73 promoter, while repressing ΔNp73 through a distinct promoter mechanism. Co-immunoprecipitation of DEC1-HDAC8, ChIP showing HDAC8 recruitment to TAp73 promoter, reporter assays PloS one High 24404147
2014 DEC1 (BHLHE40) protein stability is regulated by a dual ubiquitin-protease mechanism: SCFβTrCP ubiquitin ligase (in cooperation with CK1) targets DEC1 for proteasomal degradation during unperturbed cell cycles, while ATM/ATR-dependent DNA damage induces rapid DEC1 stabilization via the USP17 deubiquitylase, which binds and deubiquitylates DEC1. Ubiquitination assays, protein half-life measurements, Co-IP of SCFβTrCP and USP17 with DEC1, degradation-resistant mutant expression Molecular and cellular biology High 25202122
2014 Bhlhe40 (BHLHE40) functions as a cofactor of T-bet (Tbx21) on the Ifng locus in iNKT cells; Bhlhe40 accumulates at the T-box region of the Ifng locus and promotes histone H3-K9 acetylation of the Ifng locus in a T-bet-dependent manner, enhancing IFN-γ production. ChIP at Ifng locus, Bhlhe40-/- mouse model, Ifng promoter reporter assays, histone acetylation analysis Proceedings of the National Academy of Sciences High 27226296
2015 BHLHE40 and BHLHE41 suppress EMT effectors SNAI1, SNAI2, and TWIST1; BHLHE40/41 compete with the transcription factor SP1 for DNA binding at the TWIST1 promoter to regulate its basal transcriptional activity. Reporter assays with TWIST1 promoter, competition binding assays, in vitro invasion assays Molecular and cellular biology Medium 26391953
2015 Bhlhe40 (BHLHE40) binds directly to the PGC-1α C-terminal activation domain and co-occupies PGC-1α target gene promoters/enhancers, repressing PGC-1α transactivational activity by recruiting HDACs and preventing relief of PGC-1α intramolecular repression. Co-immunoprecipitation of Bhlhe40-PGC-1α, ChIP at target promoters, HDAC recruitment assays, siRNA knockdown Molecular and cellular biology High 25963661
2015 Hypoxia induces Bhlhe40 (BHLHE40) expression via a p53-dependent but HIF1α-independent pathway; Bhlhe40 binds proximal E-boxes of the Myog promoter and reduces MyoD binding affinity and transcriptional activity, thereby inhibiting myogenic differentiation under hypoxia. Microarray analysis, ChIP at Myog promoter, Bhlhe40 overexpression/knockdown, p53-dependent pathway analysis The Journal of biological chemistry High 26468276
2015 DEC1 (BHLHE40) directly binds the E-box of the LKB1 promoter, repressing LKB1 expression; reduced LKB1 activity leads to decreased AMPK activity, establishing a DEC1→LKB1→AMPK regulatory axis. ChIP at LKB1 promoter E-box, DEC1 knockdown/overexpression, AMPK activity assays, DEC1 basic-domain mutants Biochemical and biophysical research communications Medium 26498531
2016 IL-1β induces Bhlhe40 (BHLHE40) expression in Th17 cells, defining a PTX-IL-1β-Bhlhe40 pathway; Bhlhe40 expression identifies encephalitogenic Th cells producing IFN-γ, IL-17A, and GM-CSF, and Bhlhe40-deficient Th1 and Th17 cells are nonencephalitogenic in adoptive transfer EAE. Bhlhe40 reporter mice, adoptive transfer EAE, IL-1β stimulation, cytokine analysis The Journal of experimental medicine High 26834156
2018 Bhlhe40 (BHLHE40) positively regulates IFN-γ production and negatively regulates IL-10 production in Th1 cells; Bhlhe40-mediated IFN-γ production is independent of T-bet regulation; in vivo, Bhlhe40-deficient mice succumb to Toxoplasma gondii infection and IL-10 signaling blockade rescues them. Conditional Bhlhe40 deletion in T cells, in vitro Th1 polarization, in vivo T. gondii infection model, IL-10R blockade The Journal of experimental medicine High 29773643
2018 BHLHE40 promotes HBEGF transcription by blocking DNA binding of HDAC1 and HDAC2 at the HBEGF promoter; HBEGF secreted through exosomes promotes breast cancer cell survival and migration. ChIP showing BHLHE40 at HBEGF promoter, co-immunoprecipitation of BHLHE40 with HDAC1/2, CRISPR KO, exosome analysis Breast cancer research High 30285805
2018 Bhlhe40 (BHLHE40) negatively regulates PGC-1α gene expression and the function and biogenesis of peroxisomes and mitochondria in myogenic cells; Bhlhe40 knockdown increases peroxisome number/activity but reduces mitochondrial efficiency, while overexpression of the PGC-1α-interacting domain of Bhlhe40 differentially regulates the two organelles. siRNA knockdown, overexpression, peroxisome/mitochondria counting and activity assays, gene expression profiling Redox biology Medium 30391825
2018 DEC1 (BHLHE40) and CLOCK bind E-boxes in the ATP1B1 (Na+/K+-ATPase β1 subunit) promoter; CLOCK:BMAL1 activates ATP1B1 transcription while DEC1 suppresses this transactivation, and Dec1-deficient mice show enhanced Atp1b1 expression and reduced blood pressure. ChIP and ChIP-on-chip at ATP1B1 promoter, luciferase reporter assays, Dec1-/- and Clock-mutant mice Hypertension High 30012868
2019 Bhlhe40 (BHLHE40) is required for tissue-resident memory CD8+ T cell (Trm) and tumor-infiltrating lymphocyte (TIL) development and polyfunctionality; mechanistically, Bhlhe40 sustains mitochondrial fitness and a functional epigenetic state; local PD-1 signaling inhibits TIL Bhlhe40 expression and Bhlhe40 is critical for TIL reinvigoration following anti-PD-L1 blockade. Bhlhe40 KO mouse model, mitochondrial function assays, ATAC-seq epigenetic profiling, anti-PD-L1 treatment Immunity High 31533057
2019 Bhlhe40 (BHLHE40) is required cell-intrinsically for the self-renewal and proliferation (but not polarization) of large peritoneal macrophages (LPMs); Bhlhe40 represses c-Maf and Mafb expression and directly promotes expression of cell cycle genes; Bhlhe40 binds genomic sites co-occupied by PU.1 as well as unique sites at Maf and cell-cycle loci. Bhlhe40 conditional KO, competitive reconstitution, ChIP-seq in LPMs, IL-4 proliferation assays Nature immunology High 31061528
2019 Bhlhe40 and Bhlhe41 directly repress expression of lineage-inappropriate genes in alveolar macrophages (AMs) to maintain AM identity and self-renewal; genome-wide Bhlhe40 DNA binding analysis showed direct repression of non-AM signature genes. Bhlhe40/41 double-KO mouse model, gene expression analysis, ChIP-seq/genome-wide binding characterization The EMBO journal High 31414712
2019 BHLHE40 expression in H. pylori-infected gastric epithelial cells is induced via the cagA-ERK pathway; BHLHE40 translocates to the nucleus and binds p-STAT3 (Tyr705); the BHLHE40-p-STAT3 complex increases CXCL12 expression, fostering CD4+ T cell infiltration. Co-immunoprecipitation of BHLHE40 and p-STAT3, ChIP at CXCL12 promoter, ERK pathway inhibitors FASEB journal Medium 31914631
2020 BHLHE40 (and BHLHE41) act as negative feedback regulators of TFEB transcriptional activity; high, sustained nuclear TFEB induces BHLHE40/41 expression, and BHLHE40/41 counter-regulate TFEB target genes, particularly genes relevant to lysosomal cell death. Genome-wide CRISPR screen, TFEB activation assays, gene expression analysis Cell reports Medium 33176151
2020 BHLHE40 is required in T cells for a TH2 cell transcriptional program during helminth infection, positively regulating GM-CSF (Csf2) and IL-5 production; combined loss of GM-CSF and IL-5 signaling impairs helminth protection. Bhlhe40 conditional KO in T cells, helminth infection model, cytokine gene expression analysis Journal of immunology Medium 31900338
2021 Bhlhe40 (BHLHE40) is a cell-intrinsic negative regulator of the germinal center (GC) reaction; in activated CD4 T cells it restrains proliferation limiting TFH numbers, while in B cells it selectively restricts generation of earliest GC B cells; Bhlhe40-deficient mice develop B cell lymphoma characterized by GC B-like cells. Bhlhe40-/- mouse model, flow cytometry, adoptive transfer, longitudinal lymphoma monitoring The Journal of experimental medicine High 34919144
2022 BHLHE40 directly transcriptionally regulates TAN-1 (pro-tumour neutrophil) marker genes in pancreatic cancer, downstream of hypoxia and endoplasmic reticulum stress; direct transcriptional regulation demonstrated by ChIP assay. Single-cell RNA-seq, ChIP assay, BHLHE40 overexpression in dHL-60 cells Gut Medium 35688610
2022 BHLHE40 regulates T cell-dependent anti-tumor immunity and immune checkpoint therapy (ICT) efficacy; anti-PD-1 and anti-CTLA-4 upregulate BHLHE40 in tumor antigen-specific T cells; BHLHE40-deficient T cells show dysregulated NF-κB signaling, IFNγ response, and altered chemokine/granzyme expression; BHLHE40 is required for ICT-driven macrophage polarization. Bhlhe40-/- mouse model, single-cell RNA-seq, in vivo tumor models with ICT Cancer immunology research Medium 35181783
2023 BHLHE40 regulates SREBF1 transcription as a classic transcription factor and also physically links the enhancer and promoter regions of SREBF1; the BHLHE40-SREBF1-stearoyl-CoA desaturase axis protects pancreatic cancer cells from ferroptosis by reducing lipid peroxidation. ChIP-seq, RNA-seq, Hi-C/chromosome conformation capture assays, BHLHE40 KO/overexpression Advanced science High 38064101
2023 BHLHE40 (BHLHE40) in vitro CRISPR screen identified it as a regulator of CD8+ T cell exhaustion differentiation; in vitro and in vivo validation showed BHLHE40 regulates the differentiation checkpoint between progenitor and intermediate exhausted T cell subsets. In vitro chronic stimulation model, genome-wide CRISPR screen, in vivo validation Science immunology Medium 37595022
2023 BHLHE40 represses MAFA expression by attenuating the binding of PDX1 to the Mafa enhancer region, thereby suppressing insulin secretion in hypoxic β-cells; BHLHE40 deficiency in hypoxic MIN6 cells or ob/ob β-cells reverses insulin secretion defects. BHLHE40 KO/overexpression in MIN6 cells and ob/ob mice, ChIP at Mafa enhancer, MAFA re-expression rescue EMBO reports High 37341148
2024 Loss of BHLHE40/41 in macrophages results in increased expression of DLAM (disease-associated macrophage) genes involved in cholesterol clearance and lysosomal processing, increased cholesterol efflux and storage, and increased lysosomal mass and degradative capacity, identifying BHLHE40/41 as transcriptional repressors of this activation state. BHLHE40/41 KO in iPSC-derived microglia and THP-1 macrophages; mouse Bhlhe40/41 KO; gene regulatory network reconstruction from scRNA-seq data Nature communications High 38448474

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2022 Single-cell RNA-seq analysis reveals BHLHE40-driven pro-tumour neutrophils with hyperactivated glycolysis in pancreatic tumour microenvironment. Gut 238 35688610
1997 Overexpression of Stra13, a novel retinoic acid-inducible gene of the basic helix-loop-helix family, inhibits mesodermal and promotes neuronal differentiation of P19 cells. Genes & development 223 9284045
2019 The Transcription Factor Bhlhe40 Programs Mitochondrial Regulation of Resident CD8+ T Cell Fitness and Functionality. Immunity 196 31533057
2002 Identification of functional hypoxia response elements in the promoter region of the DEC1 and DEC2 genes. The Journal of biological chemistry 194 12354771
2001 Defective T cell activation and autoimmune disorder in Stra13-deficient mice. Nature immunology 151 11668339
2014 Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation. Nature communications 149 24699451
2004 The Hand1, Stra13 and Gcm1 transcription factors override FGF signaling to promote terminal differentiation of trophoblast stem cells. Developmental biology 123 15196947
2018 The transcription factor Bhlhe40 is a switch of inflammatory versus antiinflammatory Th1 cell fate determination. The Journal of experimental medicine 113 29773643
2008 Activation of TGF-beta/activin signalling resets the circadian clock through rapid induction of Dec1 transcripts. Nature cell biology 110 19029909
2007 DEC1, a basic helix-loop-helix transcription factor and a novel target gene of the p53 family, mediates p53-dependent premature senescence. The Journal of biological chemistry 108 18025081
2006 The expression of antiapoptotic protein survivin is transcriptionally upregulated by DEC1 primarily through multiple sp1 binding sites in the proximal promoter. Oncogene 103 16462771
2003 DEC1 negatively regulates the expression of DEC2 through binding to the E-box in the proximal promoter. The Journal of biological chemistry 102 12624110
2002 Basic helix-loop-helix protein DEC1 promotes chondrocyte differentiation at the early and terminal stages. The Journal of biological chemistry 98 12384505
2014 DEC1/STRA13/SHARP2 and DEC2/SHARP1 coordinate physiological processes, including circadian rhythms in response to environmental stimuli. Current topics in developmental biology 89 25248482
2013 CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response. The Journal of experimental medicine 89 23878307
2016 DEC1 and DEC2 Crosstalk between Circadian Rhythm and Tumor Progression. Journal of Cancer 86 26819638
2016 IL-1-induced Bhlhe40 identifies pathogenic T helper cells in a model of autoimmune neuroinflammation. The Journal of experimental medicine 84 26834156
2007 Transforming growth factor-beta promotes survival of mammary carcinoma cells through induction of antiapoptotic transcription factor DEC1. Cancer research 83 17942899
2008 BHLHB2 controls Bdnf promoter 4 activity and neuronal excitability. The Journal of neuroscience : the official journal of the Society for Neuroscience 82 18234890
2008 Human mismatch repair gene, MLH1, is transcriptionally repressed by the hypoxia-inducible transcription factors, DEC1 and DEC2. Oncogene 80 18345027
2019 Bhlhe40 and Bhlhe41 transcription factors regulate alveolar macrophage self-renewal and identity. The EMBO journal 78 31414712
2003 The transcriptional repressor STRA13 regulates a subset of peripheral circadian outputs. The Journal of biological chemistry 72 14581485
2012 The BHLH transcription factor DEC1 plays an important role in the epithelial-mesenchymal transition of pancreatic cancer. International journal of oncology 71 22825629
2019 Bhlhe40 mediates tissue-specific control of macrophage proliferation in homeostasis and type 2 immunity. Nature immunology 67 31061528
2023 In vitro modeling of CD8+ T cell exhaustion enables CRISPR screening to reveal a role for BHLHE40. Science immunology 66 37595022
2006 Hypoxic repression of STAT1 and its downstream genes by a pVHL/HIF-1 target DEC1/STRA13. Oncogene 66 16878149
2007 Stra13 regulates satellite cell activation by antagonizing Notch signaling. The Journal of cell biology 65 17502421
2013 Sunitinib induces cellular senescence via p53/Dec1 activation in renal cell carcinoma cells. Cancer science 61 23578198
2004 Rhythmic expression of DEC1 and DEC2 in peripheral tissues: DEC2 is a potent suppressor for hepatic cytochrome P450s opposing DBP. Genes to cells : devoted to molecular & cellular mechanisms 58 15066123
2008 Stra13/DEC1 and DEC2 inhibit sterol regulatory element binding protein-1c in a hypoxia-inducible factor-dependent mechanism. Nucleic acids research 56 18838394
2004 STRA13 interacts with STAT3 and modulates transcription of STAT3-dependent targets. Journal of molecular biology 55 15223310
2011 Basic helix-loop-helix transcription factor DEC1 negatively regulates cyclin D1. The Journal of pathology 53 21506129
2018 BHLHE40 confers a pro-survival and pro-metastatic phenotype to breast cancer cells by modulating HBEGF secretion. Breast cancer research : BCR 51 30285805
2008 Regulation of lipogenesis via BHLHB2/DEC1 and ChREBP feedback looping. Biochemical and biophysical research communications 50 18602890
2010 The role of the basic helix-loop-helix transcription factor Dec1 in the regulatory T cells. Journal of immunology (Baltimore, Md. : 1950) 48 21057086
2006 SHARP2: protein-protein interaction predictions using patch analysis. Bioinformatics (Oxford, England) 48 16672257
2011 Basic helix-loop-helix transcription factors DEC1 and DEC2 regulate the paclitaxel-induced apoptotic pathway of MCF-7 human breast cancer cells. International journal of molecular medicine 46 21327324
2000 Isolation and mutational analysis of a novel human cDNA, DEC1 (deleted in esophageal cancer 1), derived from the tumor suppressor locus in 9q32. Genes, chromosomes & cancer 46 10612805
2020 TFEB Transcriptional Responses Reveal Negative Feedback by BHLHE40 and BHLHE41. Cell reports 45 33176151
2012 Clonal B cells of HCV-associated mixed cryoglobulinemia patients contain exhausted marginal zone-like and CD21 low cells overexpressing Stra13. European journal of immunology 44 22678901
2015 Regulation of the Mechanism of TWIST1 Transcription by BHLHE40 and BHLHE41 in Cancer Cells. Molecular and cellular biology 42 26391953
2016 Transcriptional regulator Bhlhe40 works as a cofactor of T-bet in the regulation of IFN-γ production in iNKT cells. Proceedings of the National Academy of Sciences of the United States of America 41 27226296
2015 Hypoxia Inhibits Myogenic Differentiation through p53 Protein-dependent Induction of Bhlhe40 Protein. The Journal of biological chemistry 41 26468276
2005 Tissue-specific disruption of rhythmic expression of Dec1 and Dec2 in clock mutant mice. Journal of biological rhythms 40 16267380
2004 DNA binding, but not interaction with Bmal1, is responsible for DEC1-mediated transcription regulation of the circadian gene mPer1. The Biochemical journal 40 15193144
2001 Induction of basic helix-loop-helix protein DEC1 (BHLHB2)/Stra13/Sharp2 in response to the cyclic adenosine monophosphate pathway. European journal of cell biology 39 11432722
2024 BHLHE40/41 regulate microglia and peripheral macrophage responses associated with Alzheimer's disease and other disorders of lipid-rich tissues. Nature communications 38 38448474
2024 Single-Cell and Spatial Transcriptome Profiling Identifies the Transcription Factor BHLHE40 as a Driver of EMT in Metastatic Colorectal Cancer. Cancer research 38 38657117
2020 Non-circadian aspects of BHLHE40 cellular function in cancer. Genes & cancer 38 32577154
2007 Stra13 is induced by genotoxic stress and regulates ionizing-radiation-induced apoptosis. EMBO reports 38 17347673
2022 BHLHE40 Regulates the T-Cell Effector Function Required for Tumor Microenvironment Remodeling and Immune Checkpoint Therapy Efficacy. Cancer immunology research 37 35181783
2011 SUMOylation of DEC1 protein regulates its transcriptional activity and enhances its stability. PloS one 37 21829689
2005 Tumor suppressive role of a 2.4 Mb 9q33-q34 critical region and DEC1 in esophageal squamous cell carcinoma. Oncogene 37 15580306
2018 The bHLH transcription factor DEC1 promotes thyroid cancer aggressiveness by the interplay with NOTCH1. Cell death & disease 36 30158530
2005 Association, mutual stabilization, and transcriptional activity of the STRA13 and MSP58 proteins. Cellular and molecular life sciences : CMLS 34 15719173
2018 Dec1 and CLOCK Regulate Na+/K+-ATPase β1 Subunit Expression and Blood Pressure. Hypertension (Dallas, Tex. : 1979) 33 30012868
2014 Stra13 and Sharp-1, the non-grouchy regulators of development and disease. Current topics in developmental biology 33 25248481
2014 DEC1 coordinates with HDAC8 to differentially regulate TAp73 and ΔNp73 expression. PloS one 32 24404147
2002 Clast5/Stra13 is a negative regulator of B lymphocyte activation. Biochemical and biophysical research communications 32 11890681
2021 Bhlhe40 function in activated B and TFH cells restrains the GC reaction and prevents lymphomagenesis. The Journal of experimental medicine 31 34919144
2017 DEC1 is required for anti-apoptotic activity of gastric cancer cells under hypoxia by promoting Survivin expression. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 31 29204860
2012 Differentiated embryo chondrocyte 1 (DEC1) represses PPARγ2 gene through interacting with CCAAT/enhancer binding protein β (C/EBPβ). Molecules and cells 31 22610404
2021 Antigen-driven PD-1+ TOX+ BHLHE40+ and PD-1+ TOX+ EOMES+ T lymphocytes regulate juvenile idiopathic arthritis in situ. European journal of immunology 30 33296081
2014 USP17- and SCFβTrCP--regulated degradation of DEC1 controls the DNA damage response. Molecular and cellular biology 30 25202122
2011 DeltaNp63, a target of DEC1 and histone deacetylase 2, modulates the efficacy of histone deacetylase inhibitors in growth suppression and keratinocyte differentiation. The Journal of biological chemistry 30 21317427
2020 BHLHE40 Promotes TH2 Cell-Mediated Antihelminth Immunity and Reveals Cooperative CSF2RB Family Cytokines. Journal of immunology (Baltimore, Md. : 1950) 29 31900338
2014 Mice lacking the circadian modulators SHARP1 and SHARP2 display altered sleep and mixed state endophenotypes of psychiatric disorders. PloS one 29 25340473
2004 Impaired lymphocyte development and function in Clast5/Stra13/DEC1-transgenic mice. European journal of immunology 29 15114665
2023 BHLHE40 Inhibits Ferroptosis in Pancreatic Cancer Cells via Upregulating SREBF1. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 28 38064101
2008 Liver X receptors (LXRalpha and LXRbeta) are potent regulators for hepatic Dec1 expression. Genes to cells : devoted to molecular & cellular mechanisms 28 19032342
2022 Dec1 Deficiency Ameliorates Pulmonary Fibrosis Through the PI3K/AKT/GSK-3β/β-Catenin Integrated Signaling Pathway. Frontiers in pharmacology 27 35355710
2020 LncRNA-ES3 inhibition by Bhlhe40 is involved in high glucose-induced calcification/senescence of vascular smooth muscle cells. Annals of the New York Academy of Sciences 27 32483833
2003 Stra13, a prostaglandin E2-induced gene, regulates the cellular redox state of podocytes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 12594185
2020 Long noncoding RNA BHLHE40-AS1 promotes early breast cancer progression through modulating IL-6/STAT3 signaling. Journal of cellular biochemistry 26 31907974
2015 DEC1 negatively regulates AMPK activity via LKB1. Biochemical and biophysical research communications 26 26498531
2004 Dec1 and Dec2 expression is disrupted in the suprachiasmatic nuclei of Clock mutant mice. Journal of biological rhythms 26 15038852
2023 Hypoxia causes pancreatic β-cell dysfunction and impairs insulin secretion by activating the transcriptional repressor BHLHE40. EMBO reports 24 37341148
2018 Bhlhe40 differentially regulates the function and number of peroxisomes and mitochondria in myogenic cells. Redox biology 24 30391825
2012 Regulation of basic helix-loop-helix transcription factors Dec1 and Dec2 by RORα and their roles in adipogenesis. Genes to cells : devoted to molecular & cellular mechanisms 24 22244086
2024 Empagliflozin ameliorates vascular calcification in diabetic mice through inhibiting Bhlhe40-dependent NLRP3 inflammasome activation. Acta pharmacologica Sinica 23 38172306
2012 SUMO modification of Stra13 is required for repression of cyclin D1 expression and cellular growth arrest. PloS one 23 22905217
2001 Cross-regulatory interaction between Stra13 and USF results in functional antagonism. Oncogene 22 11498797
2022 Obstructive sleep apnea-increased DEC1 regulates systemic inflammation and oxidative stress that promotes development of pulmonary arterial hypertension. Apoptosis : an international journal on programmed cell death 20 36484960
2021 BHLHE40 Regulates IL-10 and IFN-γ Production in T Cells but Does Not Interfere With Human Type 1 Regulatory T Cell Differentiation. Frontiers in immunology 20 34305917
2018 Clusterin, a Novel DEC1 Target, Modulates DNA Damage-Mediated Cell Death. Molecular cancer research : MCR 20 30002194
2013 Hypoxia-induced overexpression of DEC1 is regulated by HIF-1α in hepatocellular carcinoma. Oncology reports 20 24100543
2009 P/CAF rescues the Bhlhe40-mediated repression of MyoD transactivation. The Biochemical journal 20 19522704
2020 Dec1 deficiency protects the heart from fibrosis, inflammation, and myocardial cell apoptosis in a mouse model of cardiac hypertrophy. Biochemical and biophysical research communications 19 32896382
2015 Bhlhe40 Represses PGC-1α Activity on Metabolic Gene Promoters in Myogenic Cells. Molecular and cellular biology 19 25963661
2018 Mice lacking the transcriptional regulator Bhlhe40 have enhanced neuronal excitability and impaired synaptic plasticity in the hippocampus. PloS one 18 29715265
2017 Downregulation of DEC1 contributes to the neurotoxicity induced by MPP+ by suppressing PI3K/Akt/GSK3β pathway. CNS neuroscience & therapeutics 18 28734031
2019 Upexpression of BHLHE40 in gastric epithelial cells increases CXCL12 production through interaction with p-STAT3 in Helicobacter pylori-associated gastritis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 31914631
2018 Transcription factor DEC1 is required for maximal experimentally induced periodontal inflammation. Journal of periodontal research 17 29882288
2023 Promotion of colorectal cancer by transcription factor BHLHE40 involves upregulation of ADAM19 and KLF7. Frontiers in oncology 16 36890812
2022 Upregulation of INHBA mediated by the transcription factor BHLHE40 promotes colon cancer cell proliferation and migration. Journal of clinical laboratory analysis 16 35689549
2020 Thyroid hormone induces cellular senescence in prostate cancer cells through induction of DEC1. The Journal of steroid biochemistry and molecular biology 16 32360904
2015 Basic helix-loop-helix transcription factor DEC1 regulates the cisplatin-induced apoptotic pathway of human esophageal cancer cells. Biomedical research (Tokyo, Japan) 16 25876658
2022 DEC1 promotes progression of Helicobacter pylori-positive gastric cancer by regulating Akt/NF-κB pathway. Journal of cellular and molecular medicine 15 35122398
2006 Molecular analysis of Dec1 and Dec2 in the peripheral circadian clock of zebrafish photosensitive cells. Biochemical and biophysical research communications 15 17097613
2022 Long noncoding RNA SNHG1 alleviates high glucose-induced vascular smooth muscle cells calcification/senescence by post-transcriptionally regulating Bhlhe40 and autophagy via Atg10. Journal of physiology and biochemistry 14 36194366