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Showing BHLHE40 — STRA13 is a alias.

BHLHE40

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

Length
412 aa
Mass
45.5 kDa
Annotated
2026-06-09
100 papers in source corpus 47 papers cited in narrative 47 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BHLHE40 (also DEC1/SHARP-2/BHLHB2) is a basic helix-loop-helix transcription factor that operates as both a direct repressor and a context-dependent activator, integrating immune, metabolic, circadian, and developmental gene programs through E-box binding and through protein-protein interactions that redirect it to non-E-box loci (PMID:18234890, PMID:25963661, PMID:26391953). In the immune system it is a master rheostat of cytokine output: it is required cell-intrinsically in T cells to promote GM-CSF and IFN-γ while repressing IL-10, and IL-10 derepression accounts for the impaired pathogen control and altered autoimmunity of Bhlhe40-deficient animals across EAE, Toxoplasma, and tuberculosis models (PMID:24699451, PMID:29773643, PMID:29773644). It acts as a T-bet cofactor that accumulates at the Ifng locus and drives histone acetylation (PMID:27226296), directly binds Th1 cis-elements (Tbx21, Cxcr6) to activate them while repressing Tfh genes (Bcl6, Cxcr5) (PMID:38619295, PMID:41134666), and is required for tissue-resident/tumor-infiltrating CD8+ T-cell mitochondrial fitness, epigenetic state, and the differentiation checkpoint between exhausted subsets, making it central to anti-tumor immunity and checkpoint-blockade responsiveness (PMID:31533057, PMID:37595022). In myeloid lineages BHLHE40 (with BHLHE41) enforces tissue-resident and alveolar macrophage identity and self-renewal by directly repressing lineage-inappropriate factors c-Maf and Mafb and promoting cell-cycle genes (PMID:31061528, PMID:31414712). Across metabolism it represses PGC-1α transactivation via HDAC recruitment to control mitochondrial and peroxisomal function (PMID:25963661), serves as a required cofactor with C/EBPβ and LXRα for insulin-induced hepatic SREBP-1c (PMID:29952285), and controls lipogenic and ferroptosis-protective programs including direct, enhancer-promoter looping regulation of SREBF1 (PMID:18602890, PMID:38064101). It contributes negative-feedback control of the circadian clock with tissue-specific repressor/coactivator behavior (PMID:18648504) and represses neuronal Bdnf to set seizure threshold (PMID:18234890). In numerous tissues BHLHE40 governs differentiation and proliferation through direct targets such as MyoD-dependent myogenic genes (PMID:19522704, PMID:26468276), osteoclast factors Fos/Nfatc1 (PMID:35619122), and trophoblast programs via interaction with GATA2/3 (PMID:40911186).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2001 Medium

    Establishing how BHLHE40 is induced was the entry point to understanding its signaling context; this work defined it as an immediate-early transcriptional target of cAMP signaling.

    Evidence Transcription/protein-synthesis inhibitor dissection across multiple cell types

    PMID:11432722

    Open questions at the time
    • No ChIP confirmation of the regulatory element
    • Did not connect induction to a downstream function
  2. 2002 Medium

    Linking BHLHE40's DNA-binding activity to cell fate, this work showed its repressor function controls proliferation and selectively blocks mitochondrial (intrinsic) apoptosis.

    Evidence Inducible stable expression with DNA-binding mutant and procaspase activity assays under serum deprivation

    PMID:12119049

    Open questions at the time
    • No direct target genes identified
    • Mechanism of caspase 3/7/9 selectivity unresolved
  3. 2008 High

    Three studies established BHLHE40 as a direct sequence-specific repressor in distinct tissues, defining its biochemical mode and circadian role.

    Evidence EMSA/ChIP at Bdnf promoter 4 with KO seizure phenotype; ChoRE promoter mapping with ChREBP feedback loop; single/double KO circadian behavioral and clock-gene analysis

    PMID:18234890 PMID:18602890 PMID:18648504

    Open questions at the time
    • Cofactor requirements for repression not defined
    • Context determinants of repressor vs coactivator behavior in the clock unclear
  4. 2009 High

    Resolving how BHLHE40 controls muscle gene programs, this work showed it binds the PGC-1α promoter E-box, complexes with MyoD, and is relieved by P/CAF, establishing a cofactor-competition mechanism.

    Evidence EMSA, Co-IP, ChIP, and luciferase reporter with P/CAF dose-response in myogenic cells

    PMID:19522704

    Open questions at the time
    • In vivo relevance to muscle differentiation not tested
    • Single locus focus
  5. 2014 High

    This established BHLHE40's defining immunological role: cell-intrinsic control of the GM-CSF/IL-10 balance that sets autoreactive T-cell pathogenicity.

    Evidence KO mice, T-cell rescue, and IL-10 receptor blockade epistasis in EAE

    PMID:24699451

    Open questions at the time
    • Direct transcriptional targets at Il10/Csf2 not yet mapped
    • Mechanism distinguishing repression vs activation unclear
  6. 2015 High

    These studies dissected the BHLHE40–PGC-1α metabolic axis, showing direct binding, HDAC-mediated repression of PGC-1α transactivation, and consequences for mitochondria, peroxisomes, and ROS.

    Evidence Co-IP, ChIP, siRNA knockdown, PGC-1α-interacting domain overexpression with metabolic/organelle readouts and exercise model; plus hypoxia/p53-driven Myog repression

    PMID:25963661 PMID:26468276

    Open questions at the time
    • Tissue-specific in vivo metabolic phenotypes incompletely defined
    • HDAC identity not specified
  7. 2015 Medium

    These works revealed BHLHE40 can act through SP1 rather than its own E-box, repressing EMT regulators and tumor invasion.

    Evidence Luciferase, ChIP, SP1 siRNA epistasis, and invasion assays for TWIST1/SNAI1/SNAI2 suppression

    PMID:26391953

    Open questions at the time
    • In vivo tumor relevance limited
    • Generalizability of SP1-tethering mechanism not established
  8. 2016 High

    These studies extended BHLHE40's immune role upstream and downstream: IL-1β induces it to confer encephalitogenicity, and it acts as a T-bet cofactor at the Ifng locus.

    Evidence Reporter mice with adoptive transfer and IL-1R blockade; ChIP at Ifng T-box with H3K9ac and reporter assays in iNKT cells

    PMID:26834156 PMID:27226296

    Open questions at the time
    • Direct vs cofactor-dependent binding modes not fully separated
    • Structural basis of T-bet cooperation unknown
  9. 2018 High

    A cluster of studies cemented BHLHE40 as the key transcription factor repressing IL-10 during infection and as a metabolic cofactor, while expanding its activator/repressor repertoire.

    Evidence Conditional and double-KO epistasis in Toxoplasma and M. tuberculosis; reciprocal Co-IP with C/EBPβ and LXRα for SREBP-1c induction; ChIP/Co-IP at HBEGF and CLDN1 via HDAC and SP1

    PMID:29704436 PMID:29773643 PMID:29773644 PMID:29952285 PMID:30285805

    Open questions at the time
    • How a single factor switches between repression and activation context-dependently remains unresolved
    • Direct Il10 promoter occupancy mechanism in T cells not detailed
  10. 2019 High

    These studies defined BHLHE40's role in maintaining tissue-resident myeloid and lymphoid cell identity, fitness, and self-renewal through direct genomic occupancy.

    Evidence Competitive KO with ChIP-seq in large peritoneal and alveolar macrophages (c-Maf/Mafb repression, cell-cycle gene activation); KO with metabolic and epigenetic profiling plus anti-PD-L1 in Trm/TIL

    PMID:31061528 PMID:31414712 PMID:31533057

    Open questions at the time
    • How PD-1 signaling suppresses Bhlhe40 mechanistically unclear
    • Determinants of locus-specific repression vs activation in macrophages not defined
  11. 2020 Medium

    A CRISPR screen positioned BHLHE40/41 as a negative-feedback arm opposing TFEB during lysosomal stress.

    Evidence Genome-wide CRISPR screen with TFEB localization control and lysosomal cell-death assays

    PMID:33176151

    Open questions at the time
    • Direct target genes counter-regulated not mapped
    • Single-lab functional validation
  12. 2021 Medium

    These works expanded post-transcriptional and germinal-center control, and a tumor-suppressor link, showing lncRNA-mediated stabilization/SUMOylation and GC-restraining functions.

    Evidence RNA pull-down/RIP and SUMOylation Co-IP for SNHG1-PIAS3-Bhlhe40 in VSMC; KO immunization with GC B/TFH flow and aging lymphoma phenotype; Sirt1 promoter reporter in neural stem cells

    PMID:33987177 PMID:34919144 PMID:36194366

    Open questions at the time
    • Physiological role of Bhlhe40 SUMOylation unclear
    • Mechanism of GC lymphoma development not defined
  13. 2022 Medium

    These studies extended BHLHE40 to bone, cardiac, and alloimmune disease through direct target genes and signaling outputs.

    Evidence ChIP at Fos/Nfatc1 with KO bone phenotype; cardiac-specific KD with NF-κB/NLRP3 and TGF-β1 readouts; KO GVHD model with GM-CSF/DC activation

    PMID:31880771 PMID:35619122 PMID:36304536

    Open questions at the time
    • Direct vs indirect signaling effects in cardiac AF not separated
    • Generalizability across tissues uncertain
  14. 2023 High

    These studies sharpened BHLHE40's role in T-cell exhaustion, NK IFN-γ, β-cell insulin secretion, and drug resistance, several pinpointing indirect mechanisms (blocking another TF's binding).

    Evidence CRISPR screen defining a Tex checkpoint; STAT4/H3K4me3-driven induction and Ifng-locus ChIP in NK cells; ChIP showing attenuated PDX1 occupancy at Mafa; ChIP-seq at ABCB1 promoter; Co-IP with CCDC86 in glioma

    PMID:36931039 PMID:37341148 PMID:37595022 PMID:37830760 PMID:40837407

    Open questions at the time
    • Mechanism by which BHLHE40 displaces other transcription factors (PDX1, SP1) not structurally defined
    • Glioma CCDC86 axis lacks ChIP confirmation
  15. 2024 High

    A large body of work resolved BHLHE40 as an architectural/transcriptional regulator across lineage decisions, metabolism, and senescence, including enhancer-promoter looping and AR-dependent tumor suppression.

    Evidence ATAC/ChIP conditional KO at Th1/Tfh cis-elements; ChIP-seq + Hi-C at SREBF1 with ferroptosis assays; ChIP/enzymatic axis to PPM1F-AMPK; AR ChIP-seq/Co-IP to CCNG2 senescence; DLAM repression across microglia/macrophage models; Nrtn promoter ChIP in asthma

    PMID:38064101 PMID:38301894 PMID:38448474 PMID:38619295 PMID:38902772 PMID:40467844

    Open questions at the time
    • Genome-wide rules governing direct repression vs activation across cell types unresolved
    • Relative contribution of looping vs classic TF activity not generalized
  16. 2025 Medium

    Recent studies placed BHLHE40 in regulatory cascades (REV-ERB→Bhlhe40→c-Maf), Tfh migration circuits, and developmental differentiation via partner GATA factors.

    Evidence Epistasis with REV-ERB/c-Maf in colonic Tregs and intestinal inflammation; Bhlhe40-Pou2af1 circuit controlling CXCR5/GC migration; DNA pull-down MS/Co-IP/ChIP with GATA2/3 and CRISPR KO in trophoblast stem cells

    PMID:40911186 PMID:41134666 PMID:41359309

    Open questions at the time
    • Whether BHLHE40-GATA cooperation generalizes beyond trophoblast unknown
    • Single-lab validation for each axis

Open questions

Synthesis pass · forward-looking unresolved questions
  • The central unresolved question is the molecular logic that switches BHLHE40 between direct E-box repression, partner-tethered (SP1/T-bet/GATA) activation or repression, and chromatin-looping architecture in a cell-type-specific manner.
  • No unified model for context-dependent repressor/activator switching
  • No high-resolution structures of BHLHE40 with partners on DNA
  • Determinants of locus selection across tissues not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 5 GO:0140097 catalytic activity, acting on DNA 3
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-168256 Immune System 8 R-HSA-1430728 Metabolism 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 3 R-HSA-9909396 Circadian clock 1
Partners
CEBPBGATA2GATA3LXRAMYOD1PGC-1ΑSP1TBX21

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 Bhlhe40 is required cell-intrinsically in T cells to positively regulate GM-CSF production and negatively regulate IL-10 production; blockade of IL-10 receptor in Bhlhe40-/- mice restores EAE susceptibility, placing Bhlhe40 upstream of GM-CSF and IL-10 in autoreactive T-cell pathogenicity. Bhlhe40 knockout mice, T cell-specific rescue, IL-10 receptor blockade epistasis, in vitro cytokine assays in polarized Th1/Th17 cells Nature communications High 24699451
2018 Bhlhe40 acts as a molecular switch determining inflammatory vs. anti-inflammatory Th1 cell fate: Bhlhe40-deficient Th1 cells produce less IFN-γ and substantially more IL-10; Bhlhe40-mediated IFN-γ production is independent of T-bet regulation; IL-10 blockade rescues Bhlhe40-deficient mice from death during Toxoplasma gondii infection. Bhlhe40 conditional KO in T cells, in vitro and in vivo cytokine measurement, IL-10 signaling blockade epistasis The Journal of experimental medicine High 29773643
2018 Bhlhe40 is the first transcription factor found essential specifically to repress Il10 expression during Mycobacterium tuberculosis infection; deletion of Il10 in Bhlhe40-/- mice reverses higher bacterial burden and early lethality; Bhlhe40 deletion in T cells or CD11c+ cells is each sufficient to confer susceptibility. Bhlhe40-/- mice, Il10/Bhlhe40 double-KO epistasis, cell-type-specific deletion using Cre drivers, bacterial burden quantification The Journal of experimental medicine High 29773644
2016 Bhlhe40 expression in T cells is induced by IL-1β downstream of pertussis toxin/IL-1R signaling; Bhlhe40-expressing cells exhibit an encephalitogenic transcriptional signature; PTX co-adjuvanticity in EAE is Bhlhe40 dependent, defining a PTX–IL-1β–Bhlhe40 pathway. Bhlhe40 reporter mice, TCR-transgenic adoptive transfer, IL-1β stimulation of polarized Th17 cells, in vivo IL-1R signaling blockade The Journal of experimental medicine High 26834156
2019 Bhlhe40 is required cell-intrinsically for tissue-resident memory CD8+ T cell (Trm) and tumor-infiltrating lymphocyte (TIL) development and polyfunctionality; PD-1 signaling inhibits TIL Bhlhe40 expression; Bhlhe40 sustains mitochondrial fitness and a functional epigenetic state in Trm/TIL cells; Bhlhe40 is critical for TIL reinvigoration following anti-PD-L1 blockade. Bhlhe40 KO mice, metabolic assays, epigenetic profiling, anti-PD-L1 blockade in tumor models Immunity High 31533057
2019 Bhlhe40 is required cell-intrinsically for self-renewal and maintenance of large peritoneal macrophages (LPMs) and for their proliferation (but not polarization) in response to IL-4; Bhlhe40 directly represses c-Maf and Mafb and promotes expression of cell-cycle genes in LPMs; genome-wide ChIP shows Bhlhe40 co-occupies PU.1 sites and unique loci including Maf and cell-cycle loci. Bhlhe40 KO mice, competitive reconstitution, IL-4/helminth infection models, ChIP-seq, gene expression analysis Nature immunology High 31061528
2019 Bhlhe40 and Bhlhe41 are required for alveolar macrophage self-renewal and identity; their loss reduces AM proliferation and down-regulates AM signature genes while inducing genes of other macrophage lineages; genome-wide Bhlhe40 DNA-binding analysis shows direct repression of lineage-inappropriate genes. Bhlhe40/41 conditional KO, competitive setting, RNA-seq, ChIP-seq/genome-wide DNA binding The EMBO journal High 31414712
2018 BHLHE40 is required as a third transcription factor for insulin induction of hepatic SREBP-1c mRNA; BHLHE40 physically binds to C/EBPβ and LXRα in rat liver (co-immunoprecipitation); hepatic BHLHE40 mRNA rises rapidly upon refeeding or insulin treatment; BHLHE40 is necessary but not sufficient for SREBP-1c induction. Co-immunoprecipitation, gene knockout in mice, siRNA knockdown in hepatocytes, lentiviral overexpression, fasted/refed rat model eLife High 29952285
2016 Bhlhe40 functions as a cofactor of T-bet to enhance IFN-γ production in iNKT cells; Bhlhe40 alone has no significant effect on Ifng promoter activity but enhances T-bet-mediated Ifng promoter activation; ChIP shows Bhlhe40 accumulates at the T-box region of the Ifng locus and promotes H3K9 acetylation there in a T-bet-dependent manner. ChIP assay, Ifng promoter-luciferase reporter, Bhlhe40-deficient mice, iNKT cell functional assays Proceedings of the National Academy of Sciences of the United States of America High 27226296
2008 BHLHB2/BHLHE40 binds directly to a sequence within Bdnf promoter 4 (identified by EMSA/ChIP) and mediates transcriptional repression; NMDA receptor activation reduces BHLHB2 occupancy at promoter 4 and de-represses transcription; Bhlhb2 KO mice show increased hippocampal exon-4-specific Bdnf mRNA and increased seizure susceptibility. EMSA, ChIP in hippocampal neurons, Bhlhb2 knockout mice, NMDA stimulation, kainic acid seizure model The Journal of neuroscience High 18234890
2008 SHARP-1 and SHARP-2 (Bhlhe40) single and double mutant mice display altered circadian period length, tissue-specific clock gene expression, and entrainment kinetics; SHARP-1/2 can serve as both repressors and co-activators of mammalian clock gene expression in a context-specific manner, shown by differential Per2 amplitude changes across tissues. Sharp-1 and Sharp-2 single/double KO mice, in vivo EEG/wheel-running, light-pulse entrainment, tissue-specific clock gene expression PloS one High 18648504
2015 Bhlhe40 binds to PGC-1α directly and co-occupies PGC-1α-targeted gene promoters/enhancers to repress PGC-1α transactivational activity; repression is mediated by recruiting HDACs and preventing relief of PGC-1α intramolecular suppression; Bhlhe40 knockdown increases ROS, fatty acid oxidation, mitochondrial DNA, and PGC-1α target gene expression; exercise reduces Bhlhe40 recruitment to these loci. Co-immunoprecipitation, ChIP, siRNA knockdown, PGC-1α-interacting domain overexpression, exercise model in skeletal muscle Molecular and cellular biology High 25963661
2009 Bhlhe40 binds to the E1-box on the PGC-1α core promoter (confirmed by EMSA) and forms a complex with MyoD; Bhlhe40 represses MyoD-mediated transactivation of PGC-1α and myogenic gene promoters; P/CAF relieves this repression by interacting with Bhlhe40, thereby disrupting the P/CAF–MyoD interaction. EMSA, co-immunoprecipitation, ChIP in myogenic cells, luciferase reporter assays, P/CAF dose-response The Biochemical journal High 19522704
2015 Bhlhe40 is induced by hypoxia in satellite cell-derived primary myoblasts through a p53-dependent (HIF1α-independent) pathway; Bhlhe40 binds to proximal E-boxes of the Myog promoter, reduces MyoD binding affinity and transcriptional activity, thereby inhibiting myogenic differentiation; Bhlhe40 knockdown rescues myogenic differentiation under hypoxia. Microarray, ChIP, Bhlhe40 overexpression/knockdown, Myog promoter binding assays, HIF1α inhibition, p53 pathway analysis The Journal of biological chemistry High 26468276
2018 BHLHE40 differentially regulates peroxisome and mitochondria in myogenic cells: Bhlhe40 knockdown increases peroxisome number/activity but reduces mitochondrial efficiency and bursts ROS; a constitutively active PGC-1α-interacting domain (VBH135) of Bhlhe40 mimics peroxisome effects while simultaneously reducing ROS and increasing mitochondrial efficiency. Bhlhe40 siRNA knockdown, VBH135 constitutively-active domain overexpression, organelle activity assays, ROS measurement, fatty acid oxidation assays, gene expression profiling Redox biology Medium 30391825
2008 BHLHB2/BHLHE40 is induced by glucose and ChREBP in rat hepatocytes via a functional ChoRE element (-160 to -143 bp) in the Bhlhb2 promoter; BHLHB2 in turn binds ChoRE in Fasn, Lpk, and Bhlhb2 promoters (shown by ChIP) and represses glucose/ChREBP-mediated induction of lipogenic genes, forming a negative feedback loop with ChREBP. Promoter deletion analysis, ChIP, Bhlhb2 overexpression in hepatocytes, mRNA quantification Biochemical and biophysical research communications Medium 18602890
2002 DEC1/BHLHE40 requires its DNA-binding domain for both proliferation inhibition and anti-apoptotic activity; stable DEC1 expression selectively inhibits activation of procaspases 3, 7, and 9 (mitochondrial pathway) but not procaspase 8, blocking mitochondria-initiated apoptosis; a DNA-binding-domain mutant loses both activities. Tetracycline-inducible stable transfection, procaspase activity enzymatic assays, immunoblotting, serum deprivation apoptosis model, DNA-binding mutant The Biochemical journal Medium 12119049
2015 BHLHE40/41 suppress TWIST1 transcription by competing with SP1 for DNA binding at a critical TWIST1 promoter region; SP1 mediates basal TWIST1 transcriptional activity at the -233 to -61 bp region; BHLHE40/41 also suppress SNAI1 and SNAI2, inhibiting EMT and tumor cell invasion. Luciferase reporter assay, ChIP, BHLHE40/41 overexpression/knockdown, invasion assays, SP1 siRNA epistasis Molecular and cellular biology Medium 26391953
2018 BHLHE40 induces HBEGF transcription by blocking DNA binding of HDAC1 and HDAC2 to the HBEGF promoter (shown by ChIP and CoIP); HBEGF is secreted through exosomes and promotes breast cancer cell survival and migration; BHLHE40 knockdown/KO reduces primary tumor growth and lung metastasis in orthotopic xenograft models. ChIP, co-immunoprecipitation, shRNA knockdown, CRISPR/Cas9 KO, xenograft and metastasis models, exosome analysis Breast cancer research : BCR Medium 30285805
2018 BHLHE40 suppresses CLDN1 transcription not by direct E-box binding but by interacting with SP1 (shown by co-immunoprecipitation and co-localization) and preventing SP1 from binding a specific motif (-233 to -61 bp) in the CLDN1 promoter; the BHLH and Orange domains of BHLHE40 are both required for the BHLHE40–SP1 interaction. Co-immunoprecipitation, reporter assays, siRNA for SP1 epistasis, deletion mutagenesis of BHLHE40 domains, invasion assays Molecular carcinogenesis Medium 29704436
2023 BHLHE40 regulates a differentiation checkpoint between progenitor and intermediate exhausted CD8+ T cell (Tex) subsets; identified by genome-wide CRISPR screen in a benchmarked in vitro chronic stimulation model and validated in vivo. In vitro CRISPR pooled screen, in vitro/in vivo validation, phenotypic/transcriptional/epigenetic benchmarking Science immunology High 37595022
2023 BHLHE40 represses MAFA expression in hypoxic pancreatic β-cells by attenuating PDX1 binding to the Mafa enhancer region, thereby suppressing insulin secretion; BHLHE40 deficiency in hypoxic MIN6 cells or ob/ob mouse β-cells reverses insulin secretion defects; MAFA re-expression rescues impaired insulin secretion. BHLHE40 KO in MIN6 cells and ob/ob mice, ChIP for PDX1 occupancy, MAFA re-expression rescue, insulin secretion assays EMBO reports High 37341148
2020 BHLHE40 and BHLHE41, upregulated by high sustained nuclear TFEB, act in opposition to TFEB upon lysosomal cell death induction; BHLHE40/41 counter-regulate TFEB target genes, adding a negative feedback loop to TFEB regulatory mechanisms. Genome-wide CRISPR library screen, TFEB subcellular localization control, lysosomal cell death assays, gene expression analysis Cell reports Medium 33176151
2024 BHLHE40 regulates SREBF1 transcription both as a classic transcription factor and by physically linking SREBF1 enhancer and promoter regions; 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, BHLHE40 KO, ferroptosis assays, lipid peroxidation measurement Advanced science High 38064101
2022 Bhlhe40 is required in CD4+ T cells for GM-CSF production during graft-versus-host disease; GM-CSF (regulated by Bhlhe40) is independent of IL-6 and IL-23 signaling; mechanistically, GM-CSF produced by Bhlhe40+ T cells enhances donor dendritic cell activation in the colon, promotes indirect alloantigen presentation, and drives proinflammatory T cell accumulation. Bhlhe40 KO in GVHD model, cytokine blockade epistasis, DC activation and alloantigen presentation assays, colonic inflammation readouts Blood Medium 31880771
2021 Bhlhe40 is a cell-intrinsic negative regulator of both the B cell and T cell sides of the germinal center reaction: in activated CD4 T cells it restrains proliferation (limiting TFH numbers), and in B cells it selectively restricts generation of the earliest GC B cells; Bhlhe40-deficient mice develop B cell lymphoma with age. Bhlhe40 KO mice, immunization, flow cytometry for GC B/TFH cells, adoptive transfer, proliferation assays The Journal of experimental medicine Medium 34919144
2024 Bhlhe40 directly binds cis-regulatory elements of Th1-related genes (Tbx21, Cxcr6) to activate their expression and binds regions of Tfh-related genes (Bcl6, Cxcr5) to repress them; CD4+ T cell-specific Bhlhe40 deletion abrogates Th1 but augments Tfh differentiation and GC B cell help during LCMV infection. CD4-Cre conditional KO, epigenetic profiling (ATAC-seq/ChIP), antigen-specific T cell analysis after LCMV infection, gene expression analysis Journal of immunology High 38619295
2023 STAT4 promotes Bhlhe40 induction in NK cells during mouse CMV infection by enriching H3K4me3 at the Bhlhe40 promoter; Bhlhe40 directly promotes IFN-γ production by binding throughout the Ifng locus in activated NK cells; Bhlhe40-deficient NK cells show impaired IFN-γ production and diminished protective immunity. ChIP for STAT4 and H3K4me3 at Bhlhe40 promoter, ChIP for Bhlhe40 at Ifng locus, Bhlhe40 KO NK cell functional assays, viral challenge model Journal of immunology High 37830760
2022 Bhlhe40 promotes osteoclastogenesis by directly binding to promoter regions of c-Fos (Fos) and Nfatc1 and upregulating their expression; inhibition of Fos/Nfatc1 abrogates enhanced osteoclast differentiation induced by BHLHE40 overexpression; Bhlhe40-deficient mice have increased bone mass and decreased osteoclast bone resorption in vivo. ChIP for Bhlhe40 at Fos/Nfatc1 promoters, BHLHE40 overexpression, Bhlhe40 KO mice (micro-CT, histomorphometry), Fos/Nfatc1 inhibition epistasis Cell & bioscience Medium 35619122
2024 BHLHE40 directly suppresses PPM1F transcription; loss of Bhlhe40 leads to AMPKα dephosphorylation (via elevated PPM1F), enhanced PDHA1 Ser293 phosphorylation, and increased LDH activity, shifting metabolism toward glycolysis; the BHLHE40–PPM1F–AMPK axis thus modulates energy metabolism in endometrial cancer cells. Bhlhe40 knockdown, AMPKα phosphorylation assays, PDH/LDH activity assays, ChIP for BHLHE40 at PPM1F promoter, immunohistochemistry The Journal of biological chemistry Medium 38301894
2019 BHLHE40 in H. pylori-infected gastric epithelial cells translocates to the nucleus and binds cagA-activated p-STAT3 (Tyr705); the BHLHE40–p-STAT3 complex increases CXCL12 expression, which fosters CD4+ T cell infiltration in gastric mucosa, defining a cagA–BHLHE40–CXCL12 inflammatory axis. Co-immunoprecipitation, ChIP for BHLHE40 at CXCL12 promoter, H. pylori infection model in vivo and in vitro, cagA pathway inhibition FASEB journal Medium 31914631
2001 DEC1/BHLHE40 mRNA is rapidly and directly induced by the cAMP pathway (PTH, Bt2cAMP, forskolin) in chondrocytes and multiple cell types; actinomycin D and cycloheximide studies show the induction is at the transcriptional level and does not require new protein synthesis, identifying DEC1 as a direct cAMP target gene. Northern blot/RT-PCR in multiple cell types, actinomycin D (transcriptional inhibition), cycloheximide (protein synthesis inhibition), promoter analysis European journal of cell biology Medium 11432722
2012 BHLHE40 is a primary, dynamically regulated transcriptional target of the vitamin D receptor (VDR); the VDR binding site is located 1.7 kb upstream of the BHLHE40 transcription start site; 1α,25(OH)2D3 treatment significantly opens chromatin at this site and up-regulates BHLHE40 mRNA with a short half-life of ~0.9 h. Genome-wide VDR ChIP-seq, ATAC/open chromatin analysis, histone modification data, mRNA stability assay, trichostatin A treatment The Journal of steroid biochemistry and molecular biology Medium 23220548
2024 BHLHE40 directly binds the ABCB1 gene promoter (-1605 to -1597) and represses its transcription; BHLHE40 expression is negatively correlated with ABCB1 in cancer cells; BHLHE40 overexpression resensitizes adriamycin-resistant cells to the drug while KD induces resistance, defining BHLHE40 as a transcriptional suppressor of P-gp-mediated multidrug resistance. ChIP-seq for BHLHE40 occupancy at ABCB1 promoter, overexpression and knockdown in resistant cell lines, apoptosis and drug sensitivity assays, in vivo xenograft Neoplasia Medium 36931039
2025 BHLHE40 interacts directly with GATA2 and GATA3 to facilitate their chromatin occupancy and activates transcriptional programs essential for syncytiotrophoblast differentiation, including CGB; CRISPR/Cas9 KO of BHLHE40 in trophoblast stem cells prevents STB differentiation and impairs hormone synthesis and syncytialization. DNA pull-down coupled with mass spectrometry, Co-immunoprecipitation, CRISPR/Cas9 KO, ChIP for GATA2/3 occupancy, trophoblast differentiation assays Advanced science Medium 40911186
2025 REV-ERB promotes colonic RORγt+Foxp3+ Treg differentiation by suppressing Bhlhe40 expression; Bhlhe40 in turn inhibits c-Maf, a key factor for colonic Treg differentiation and function; the Bhlhe40–c-Maf axis also regulates IL-10 and CTLA-4 expression in Tregs, placing Bhlhe40 as a negative intermediary in the REV-ERB→Bhlhe40→c-Maf pathway. REV-ERB KO, Bhlhe40 overexpression/knockdown in Tregs, c-Maf rescue experiments, intestinal inflammation models (TNBS, oxazolone), cytokine measurement The Journal of experimental medicine Medium 41359309
2024 Loss/reduction of BHLHE40/41 in iPSC-derived microglia, THP-1 macrophages, and mouse microglia increases expression of disease-associated macrophage (DLAM) genes involved in cholesterol clearance and lysosomal processing, increases cholesterol efflux and storage, and increases lysosomal mass and degradative capacity, revealing BHLHE40/41 as repressors of the DLAM response. Gene KO/knockdown in iPSC microglia and THP-1 macrophages, mouse microglia Bhlhe40/41 KO, cholesterol efflux assays, lysosomal mass assays, transcriptomic analysis Nature communications Medium 38448474
2021 In vascular smooth muscle cells, lncRNA SNHG1 stabilizes Bhlhe40 mRNA by directly interacting with its 3'-UTR and also promotes Bhlhe40 nuclear translocation by scaffolding SUMO E3 ligase PIAS3 to facilitate Bhlhe40 SUMOylation; nuclear Bhlhe40 then suppresses Atg10 transcription to reduce autophagosome formation. RNA pull-down, RNA immunoprecipitation, RNA stability assay, luciferase reporter, co-immunoprecipitation, Western blot, Bhlhe40 knockdown/overexpression Journal of physiology and biochemistry Medium 36194366
2024 Bhlhe40 promotes alternative macrophage activation in asthma by directly binding the Neurturin (Nrtn) promoter and reducing its transcriptional activity; Bhlhe40 knockdown reduces OVA-induced lung inflammation, and simultaneous knockdown of Nrtn reverses this protective effect. Dual luciferase assay, ChIP-qPCR for Bhlhe40 at Nrtn promoter, Bhlhe40 KD in vivo and in vitro, Nrtn KD epistasis, OVA asthma model Communications biology Medium 40467844
2022 Cardiac-specific knockdown of Bhlhe40 attenuates Ang II-induced atrial fibrillation; mechanistically, Bhlhe40 KD inhibits NF-κB/NLRP3 signaling, TGF-β1/Smad2 signaling, reduces CX43 expression, and prevents Kv4.3 downregulation in atria. rAAV9-shBhlhe40 cardiac-specific KD, echocardiography, programmed electrical stimulation, histology, Western blot for signaling pathway components Frontiers in cardiovascular medicine Medium 36304536
2024 BHLHE40 is a novel direct androgen receptor (AR) target gene (shown by ChIP-seq); BHLHE40 physically interacts with AR (Co-IP) and co-translocates into the nucleus upon supraphysiological androgen (SAL) treatment; BHLHE40 mediates SAL-induced cellular senescence; downstream, BHLHE40 directly targets cyclin G2 (CCNG2) to execute senescence, defining an AR–BHLHE40–CCNG2 tumor-suppressive axis. RNA-seq, ChIP-seq (AR binding to BHLHE40 gene; BHLHE40 binding to CCNG2), Co-immunoprecipitation, nuclear translocation assay, BHLHE40 KD, in vivo xenograft Journal of experimental & clinical cancer research Medium 38902772
2021 Bhlhe40 directly binds to and negatively regulates Sirt1 promoter activity (shown by luciferase reporter); the Bhlhe40/Sirt1 axis regulates mitophagy in neural stem cells; loss of Sirt1 downstream of elevated Bhlhe40 impairs autophagy and contributes to spina bifida aperta. Luciferase reporter assay (Bhlhe40 binding to Sirt1 promoter), RNA-seq, Sirt1 activator (resveratrol) rescue, immunofluorescence for autophagy markers, ATRA-induced rat NTD model Frontiers in cell and developmental biology Medium 33987177
2013 DEC1/BHLHE40 binds directly to the promoter region of cyclin D1 in A549 lung cancer cells (shown by ChIP); DEC1 overexpression down-regulates cyclin D1, while DEC1 knockdown up-regulates it, inhibiting or promoting cell growth respectively. ChIP for DEC1 at cyclin D1 promoter, siRNA knockdown, DEC1 overexpression, colony formation and growth assays Tumour biology Medium 23423709
2025 Bhlhe40 regulates CXCR5 expression and Tfh cell migration into germinal centers by repressing Pou2af1 expression; Pou2af1 promotes Tfh formation and GC entry by upregulating CXCR5 (but not Bcl6); this Bhlhe40–Pou2af1 circuit is distinct from the Bcl6–Blimp1 fate-determination circuit. RNA-seq of antigen-specific Tfh cells in vivo (LCMV), Bhlhe40 and Pou2af1 KO/overexpression, epigenetic profiling, CXCR5 expression and GC migration assays Cell reports Medium 41134666
2023 BHLHE40 directly binds to the promoter of GRIN2D and activates its transcription in gastric cancer; BHLHE40/GRIN2D axis promotes glycolysis via p38 MAPK phosphorylation and calcium efflux; GRIN2D overexpression reverses the anti-tumor effects of BHLHE40 knockdown. ChIP for BHLHE40 at GRIN2D promoter, BHLHE40/GRIN2D KD and rescue, glycolysis assays, calcium efflux measurement, in vivo tumor model Functional & integrative genomics Medium 39546079
2024 BHLHE40 binds to the NLRP3 promoter as a negative transcriptional regulator (shown by Western blot/bioinformatics in smooth muscle cells); empagliflozin increases BHLHE40 expression to inhibit NLRP3 inflammasome activation and reduce vascular calcification; NLRP3 KO abolishes the protective effect. Western blot, bioinformatics binding analysis, NLRP3 KO mice (STZ model), db/db mouse model, EMPA treatment, high-glucose VSMC in vitro Acta pharmacologica Sinica Low 38172306
2023 In glioma, CCDC86 interacts with BHLHE40 (Co-IP) and stabilizes ATF3 expression through BHLHE40-mediated transcriptional regulation of ATF3; this CCDC86–BHLHE40–ATF3 axis activates ERK signaling and aerobic glycolysis to drive tumor progression. Co-immunoprecipitation of CCDC86 and BHLHE40, BHLHE40/ATF3 KD, ERK signaling assays, glycolysis assays, in vitro/in vivo glioma models Genes & diseases Low 40837407

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 246 35688610
2019 The Transcription Factor Bhlhe40 Programs Mitochondrial Regulation of Resident CD8+ T Cell Fitness and Functionality. Immunity 199 31533057
2014 Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation. Nature communications 151 24699451
2018 The transcription factor Bhlhe40 is a switch of inflammatory versus antiinflammatory Th1 cell fate determination. The Journal of experimental medicine 116 29773643
2018 Bhlhe40 is an essential repressor of IL-10 during Mycobacterium tuberculosis infection. The Journal of experimental medicine 101 29773644
2002 Abundant expression of Dec1/stra13/sharp2 in colon carcinoma: its antagonizing role in serum deprivation-induced apoptosis and selective inhibition of procaspase activation. The Biochemical journal 97 12119049
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
2004 The transcription factor DEC1 (stra13, SHARP2) is associated with the hypoxic response and high tumour grade in human breast cancers. British journal of cancer 87 15328513
2016 IL-1-induced Bhlhe40 identifies pathogenic T helper cells in a model of autoimmune neuroinflammation. The Journal of experimental medicine 86 26834156
2008 Disturbed clockwork resetting in Sharp-1 and Sharp-2 single and double mutant mice. PloS one 86 18648504
2008 BHLHB2 controls Bdnf promoter 4 activity and neuronal excitability. The Journal of neuroscience : the official journal of the Society for Neuroscience 82 18234890
2019 Bhlhe40 and Bhlhe41 transcription factors regulate alveolar macrophage self-renewal and identity. The EMBO journal 81 31414712
2023 In vitro modeling of CD8+ T cell exhaustion enables CRISPR screening to reveal a role for BHLHE40. Science immunology 72 37595022
2019 Bhlhe40 mediates tissue-specific control of macrophage proliferation in homeostasis and type 2 immunity. Nature immunology 68 31061528
2004 The hypoxia-regulated transcription factor DEC1 (Stra13, SHARP-2) and its expression in human tissues and tumours. The Journal of pathology 55 15221940
2018 BHLHE40 confers a pro-survival and pro-metastatic phenotype to breast cancer cells by modulating HBEGF secretion. Breast cancer research : BCR 53 30285805
2008 Regulation of lipogenesis via BHLHB2/DEC1 and ChREBP feedback looping. Biochemical and biophysical research communications 50 18602890
2013 The transcription factor DEC1 (BHLHE40/STRA13/SHARP-2) is negatively associated with TNM stage in non-small-cell lung cancer and inhibits the proliferation through cyclin D1 in A549 and BE1 cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 49 23423709
2006 SHARP2: protein-protein interaction predictions using patch analysis. Bioinformatics (Oxford, England) 48 16672257
2020 TFEB Transcriptional Responses Reveal Negative Feedback by BHLHE40 and BHLHE41. Cell reports 45 33176151
2015 Regulation of the Mechanism of TWIST1 Transcription by BHLHE40 and BHLHE41 in Cancer Cells. Molecular and cellular biology 43 26391953
2024 Single-Cell and Spatial Transcriptome Profiling Identifies the Transcription Factor BHLHE40 as a Driver of EMT in Metastatic Colorectal Cancer. Cancer research 42 38657117
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 42 27226296
2015 Hypoxia Inhibits Myogenic Differentiation through p53 Protein-dependent Induction of Bhlhe40 Protein. The Journal of biological chemistry 42 26468276
2024 BHLHE40/41 regulate microglia and peripheral macrophage responses associated with Alzheimer's disease and other disorders of lipid-rich tissues. Nature communications 40 38448474
2020 Pathogenic Bhlhe40+ GM-CSF+ CD4+ T cells promote indirect alloantigen presentation in the GI tract during GVHD. Blood 40 31880771
2020 Non-circadian aspects of BHLHE40 cellular function in cancer. Genes & cancer 39 32577154
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
2022 BHLHE40 Regulates the T-Cell Effector Function Required for Tumor Microenvironment Remodeling and Immune Checkpoint Therapy Efficacy. Cancer immunology research 38 35181783
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
2020 BHLHE40 Promotes TH2 Cell-Mediated Antihelminth Immunity and Reveals Cooperative CSF2RB Family Cytokines. Journal of immunology (Baltimore, Md. : 1950) 31 31900338
2009 The hypoxia-regulated transcription factor DEC1 (Stra13, SHARP-2) and its expression in gastric cancer. Omics : a journal of integrative biology 31 19624270
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 Mice lacking the circadian modulators SHARP1 and SHARP2 display altered sleep and mixed state endophenotypes of psychiatric disorders. PloS one 30 25340473
2023 BHLHE40 Inhibits Ferroptosis in Pancreatic Cancer Cells via Upregulating SREBF1. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 29 38064101
2004 Impaired lymphocyte development and function in Clast5/Stra13/DEC1-transgenic mice. European journal of immunology 29 15114665
2023 Hypoxia causes pancreatic β-cell dysfunction and impairs insulin secretion by activating the transcriptional repressor BHLHE40. EMBO reports 27 37341148
2020 Long noncoding RNA BHLHE40-AS1 promotes early breast cancer progression through modulating IL-6/STAT3 signaling. Journal of cellular biochemistry 27 31907974
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
2001 Gene structure and chromosomal location of a human bHLH transcriptional factor DEC1 x Stra13 x SHARP-2/BHLHB2. Journal of biochemistry 27 11226878
2018 Bhlhe40 differentially regulates the function and number of peroxisomes and mitochondria in myogenic cells. Redox biology 25 30391825
2024 Empagliflozin ameliorates vascular calcification in diabetic mice through inhibiting Bhlhe40-dependent NLRP3 inflammasome activation. Acta pharmacologica Sinica 24 38172306
2018 BHLHE40, a third transcription factor required for insulin induction of SREBP-1c mRNA in rodent liver. eLife 24 29952285
2016 Nr3C1-Bhlhb2 Axis Dysregulation Is Involved in the Development of Attention Deficit Hyperactivity. Molecular neurobiology 22 26820676
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
2012 The gene for the transcription factor BHLHE40/DEC1/stra13 is a dynamically regulated primary target of the vitamin D receptor. The Journal of steroid biochemistry and molecular biology 20 23220548
2009 P/CAF rescues the Bhlhe40-mediated repression of MyoD transactivation. The Biochemical journal 20 19522704
2018 Mice lacking the transcriptional regulator Bhlhe40 have enhanced neuronal excitability and impaired synaptic plasticity in the hippocampus. PloS one 19 29715265
2015 Bhlhe40 Represses PGC-1α Activity on Metabolic Gene Promoters in Myogenic Cells. Molecular and cellular biology 19 25963661
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
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
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 15 36194366
2020 BHLHE40 plays a pathological role in pre-eclampsia through upregulating SNX16 by transcriptional inhibition of miR-196a-5p. Molecular human reproduction 15 32579212
2019 Bhlhe40 Keeps Resident T Cells Too Fit to Quit. Immunity 15 31533052
2022 Cardiac-specific knockdown of Bhlhe40 attenuates angiotensin II (Ang II)-Induced atrial fibrillation in mice. Frontiers in cardiovascular medicine 14 36304536
2018 Interaction with SP1, but not binding to the E-box motifs, is responsible for BHLHE40/DEC1-induced transcriptional suppression of CLDN1 and cell invasion in MCF-7 cells. Molecular carcinogenesis 14 29704436
2024 Bhlhe40 deficiency attenuates LPS-induced acute lung injury through preventing macrophage pyroptosis. Respiratory research 13 38402153
2023 Steady-state memory-phenotype conventional CD4+ T cells exacerbate autoimmune neuroinflammation in a bystander manner via the Bhlhe40/GM-CSF axis. Experimental & molecular medicine 12 37121980
2022 BHLHE40 promotes osteoclastogenesis and abnormal bone resorption via c-Fos/NFATc1. Cell & bioscience 12 35619122
2021 Bhlhe40/Sirt1 Axis-Regulated Mitophagy Is Implicated in All-Trans Retinoic Acid-Induced Spina Bifida Aperta. Frontiers in cell and developmental biology 12 33987177
2012 Bhlhe40, a potential diabetic modifier gene on Dbm1 locus, negatively controls myocyte fatty acid oxidation. Genes & genetic systems 12 23229312
2019 Mutual suppression between BHLHE40/BHLHE41 and the MIR301B-MIR130B cluster is involved in epithelial-to-mesenchymal transition of endometrial cancer cells. Oncotarget 10 31384392
2009 SHARP-2 gene silencing by lentiviral-based short hairpin RNA interference prolonged rat kidney transplant recipients' survival time. The Journal of international medical research 10 19589260
2021 17β-Estradiol Inhibits Proliferation and Oxidative Stress in Vascular Smooth Muscle Cells by Upregulating BHLHE40 Expression. Frontiers in cardiovascular medicine 9 34917665
2024 The clock gene BHLHE40 and atypical CCNG2 control androgen-induced cellular senescence as a novel tumor suppressive pathway in prostate cancer. Journal of experimental & clinical cancer research : CR 8 38902772
2023 Overcoming ABCB1-mediated multidrug resistance by transcription factor BHLHE40. Neoplasia (New York, N.Y.) 8 36931039
2023 BHLHE40, a potential immune therapy target, regulated by FGD5-AS1/miR-15a-5p in pancreatic cancer. Scientific reports 8 37773521
2022 REL and BHLHE40 Variants Are Associated with IL-12 and IL-10 Responses and Tuberculosis Risk. Journal of immunology (Baltimore, Md. : 1950) 8 35217585
2022 MiR-494-3p Upregulation Exacerbates Cerebral Ischemia Injury by Targeting Bhlhe40. Yonsei medical journal 8 35352891
2025 Icaritin induces paraptosis in hepatocellular carcinoma cells by targeting BHLHE40 via endoplasmic reticulum stress and mitochondrial dysfunction. Phytomedicine : international journal of phytotherapy and phytopharmacology 7 40424981
2024 BHLHE40-mediated transcriptional activation of GRIN2D in gastric cancer is involved in metabolic reprogramming. Functional & integrative genomics 7 39546079
2024 Vitamin a potentiates sheep myoblasts myogenic differentiation through BHLHE40-modulated ID3 expression. BMC genomics 6 38443816
2024 Bhlhe40 Promotes CD4+ T Helper 1 Cell and Suppresses T Follicular Helper Cell Differentiation during Viral Infection. Journal of immunology (Baltimore, Md. : 1950) 6 38619295
2023 Cutting Edge: STAT4 Promotes Bhlhe40 Induction to Drive Protective IFN-γ from NK Cells during Viral Infection. Journal of immunology (Baltimore, Md. : 1950) 6 37830760
2022 A novel role of helix-loop-helix transcriptional factor Bhlhe40 in osteoclast activation. Journal of cellular physiology 6 35908202
2024 Bhlhe40 Regulates Proliferation and Angiogenesis in Mouse Embryoid Bodies under Hypoxia. International journal of molecular sciences 5 39062912
2024 Long non-coding RNA NEAT1 induced by BHLHE40 activates Wnt/β-catenin signaling and potentiates colorectal cancer progression. Cell division 5 39098910
2023 BHLHE40/41 regulate macrophage/microglia responses associated with Alzheimer's disease and other disorders of lipid-rich tissues. bioRxiv : the preprint server for biology 5 36824752
2023 BHLHE40 Mediates Cross-Talk between Pathogenic TH17 Cells and Myeloid Cells during Experimental Autoimmune Encephalomyelitis. ImmunoHorizons 5 37934060
2016 Induction of the SHARP-2 mRNA level by insulin is mediated by multiple signaling pathways. Bioscience, biotechnology, and biochemistry 5 27792527
2025 Integrated analysis of scRNA-seq and bulk RNA-seq data identifies BHLHE40 as a key gene in pancreatic cancer progression and gemcitabine resistance. Seminars in oncology 4 40250076
2025 IL-18 drives the Bhlhe40-mediated pathogenic Th17 cell response and exacerbates autoimmune disease progression. Cellular & molecular immunology 4 41087718
2023 Bhlhe40 limits early IL-10 production from CD4+ T cells during Plasmodium yoelii 17X infection. Infection and immunity 4 37843306
2023 LncRNA H19 Influences Cellular Activities via the miR-454-3p/BHLHE40 Axis in Anaplastic Thyroid Carcinoma. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 4 38052232
2012 Analysis of regulatory mechanisms of an insulin-inducible SHARP-2 gene by (S)-Equol. Archives of biochemistry and biophysics 4 22683650
2012 Analysis of induction mechanisms of an insulin-inducible transcription factor SHARP-2 gene by (-)-epigallocatechin-3-gallate. Journal of agricultural and food chemistry 4 22967044
2024 The BHLHE40‒PPM1F‒AMPK pathway regulates energy metabolism and is associated with the aggressiveness of endometrial cancer. The Journal of biological chemistry 3 38301894
2021 BHLHE40 modulates post-traumatic stress disorder behaviors with the involvement of the PI3K/AKT signaling pathway. Anais da Academia Brasileira de Ciencias 3 34161515
2025 BHLHE40 contributes to allergic asthma progression in mice through NRTN downregulation in macrophages. Communications biology 2 40467844
2025 CCDC86-BHLHE40-ATF3 axis promotes aerobic glycolysis and tumor development in glioma. Genes & diseases 2 40837407
2024 BHLHE40 Regulates Myeloid Cell Polarization through IL-10-Dependent and -Independent Mechanisms. Journal of immunology (Baltimore, Md. : 1950) 2 38683120
2024 BHLHE40 regulates microglia polarization after spinal cord injury via the NF-κB pathway. Brain research bulletin 2 39586332
2023 In Vitro Modeling of CD8 T Cell Exhaustion Enables CRISPR Screening to Reveal a Role for BHLHE40. bioRxiv : the preprint server for biology 2 37131713
2023 BHLHE40 Maintains the Stemness of PαS Cells In Vitro by Targeting Zbp1 through the Wnt/β-Catenin Signaling Pathway. Biomedicines 2 37626688
2025 Single cell RNA-sequencing reveals BHLHE40 and NDRG1 as key regulatory molecules modulating the trophoblastic senescence in preeclampsia. Placenta 1 40517485
2025 BHLHE40 Cooperates with GATA2/3 to Control Human Syncytiotrophoblast Lineage Differentiation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 40911186
2025 Optimal CXCR5 expression during Tfh maturation involves the Bhlhe40-Pou2af1 axis. Cell reports 1 41134666
2025 REV-ERB regulates RORγt+ regulatory T cell specification and function through the Bhlhe40-c-Maf axis. The Journal of experimental medicine 1 41359309

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