Ask about this productRelated genes to: SETDB1 antibody
- Gene:
- SETDB1 NIH gene
- Name:
- SET domain bifurcated histone lysine methyltransferase 1
- Previous symbol:
- -
- Synonyms:
- KG1T, KIAA0067, ESET, KMT1E, TDRD21
- Chromosome:
- 1q21.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-07-19
- Date modifiied:
- 2018-12-21
Related products to: SETDB1 antibody
Related articles to: SETDB1 antibody
- Alcohol-associated liver disease (ALD) progresses from steatosis to steatohepatitis, but the underlying mechanisms remain unclear. Here, we investigated SETDB1's role in ALD progression involving LC3B-mediated LC3-associated phagocytosis (LAP). SETDB1 expression was progressively downregulated in livers of alcohol-fed mice and ethanol-treated hepatocytes, correlating with disease severity. Setdb1 HKO mice exhibited accelerated ALD progression, developing severe steatosis, inflammation, and fibrosis even under pair-fed conditions, indicating SETDB1 deficiency enhances disease susceptibility to nutritional stressors. Mechanistically, SETDB1 acted as a transcriptional cofactor for ERG to promote Map1lc3b transcription. SETDB1 deficiency impaired LAP by disrupting Rubicon membrane localization, causing defective lipid droplet clearance and enhanced cGAS-STING activation. The ATG16L1 WD40 domain was essential for this LAP-mediated protection. LC3B restoration in Setdb1 HKO mice ameliorated steatosis, inflammation, and liver injury. Notably, the lipidation-deficient LC3B-G120A mutant failed to rescue steatosis but partially suppressed inflammation, revealing a lipidation-independent LC3B function. We demonstrate lipidated LC3B mediates cytoplasmic LAP-dependent lipid clearance, while non-lipidated LC3B translocates to the nucleus, reducing R-loop accumulation, preserving genomic stability, and restraining cGAS-STING-driven inflammation. Collectively, these findings define a protective SETDB1-ERG-LC3B axis restraining ALD progression and reveal dual LC3B functions, offering mechanistic insight and a potential therapeutic strategy for intercepting steatosis-to-steatohepatitis transition. - Source: PubMed
Publication date: 2026/05/19
Zhang YiWei TanWu JiahangLin ChuixuZhu DongboLi YanhuiShi ShutingHuang ShishunJiang LeimingWang HongzhiSong MeiqiGao PengfeiWu XuFan MingjianWei ChaofengWang QianQu LihuiWang Zhigang - Histone H3K9me3 silences repetitive elements and represses non-lineage genes during early development, but its role in organogenesis is understudied. Here, we show that H3K9me3 deposition is dynamic during epidermis morphogenesis and essential for lineage diversification. We ablate Suv39h1, Suv39h2, and Setdb1 histone methyltransferases, in the embryonic mouse epidermis, to induce H3K9me3 loss. This causes complete failure of keratinocyte differentiation, skin barrier formation, hair follicle development, and Merkel cell specification. Single-cell transcriptomics reveals aberrant cell fates with mixed epidermal subtype identities and dysregulated non-lineage and lineage-specific transcription programs. Affected pathways include differentiation, metabolism, cell cycle, cytoskeletal organization, and extracellular matrix. H3K9me3 primarily restricts RNA Pol II transcription initiation at key developmental promoters and enhancers and has minimal direct effect on promoter-proximal pause release. We uncover a cooperative and indispensable role for Suv39h1, Suv39h2, and Setdb1 in gene expression control of epidermal morphogenesis, establishing H3K9me3 as a critical developmental determinant of skin organogenesis. - Source: PubMed
Publication date: 2026/05/15
Bai Chris KeChovatiya GopalPollack Emily JanineLiao Yu-ChingKim Ashley NayeonTumbar Tudorita - Human endogenous retroviruses (HERVs) represent 8% of our genome. They are remnants of ancient infections of germinal cells. HERVs are no longer infectious, but their enhanced expression is implicated in several diseases, including neuropsychiatric disorders. Their transcription is regulated by and , which are involved in the regulation of epigenetic processes, in neural cell differentiation, and brain inflammation. We explored the expressions of HERVs and / in adolescents affected by anorexia nervosa (AN). Through real-time PCR, we assessed the transcription levels of genes of HERV-H, -K, and -W, of genes of Syncytin 1 (SYN1), Syncytin 2 (SYN2), and of HERV-W, and of and in whole blood of 37 adolescents with AN and in healthy controls (HCs) of comparable age. , and transcriptional levels were significantly higher in adolescents with AN as compared with HCs, while HERV-W- and - were downregulated in the former. No differences were observed for SYN1, SYN2, and between the two groups. The observed expression pattern of HERVs is specific for AN as compared to other neuropsychiatric disorders. These aberrant expressions suggest a potential role of retroviral elements in the pathophysiology of AN, opening the way for innovative diagnostic and therapeutic strategies. - Source: PubMed
Publication date: 2026/04/23
Amianto FedericoTovo Pier-AngeloPo AliceCalvi CristinaDavico ChiaraMontanari PaolaRainò ElenaAnichini AntonellaVesco SerenaBechis DanielaMarotta CristinaGambarino StefanoGalliano IlariaBergallo Massimiliano - Duchenne muscular dystrophy (DMD) is an incurable muscle-wasting disorder characterized by chronic membrane damage, inflammation, and progressive fibrosis. Fibrosis in DMD is driven by sustained TGFβ signaling, which promotes extracellular matrix (ECM) accumulation. We previously showed that SETDB1 sustains the TGFβ-induced fibrotic response in DMD myotubes. Here, we further show that SETDB1 modulates the TGFβ-induced secretome, particularly by regulating ECM-related proteins. Comparison of the basal secretome from DMD patient-derived myotubes and healthy controls revealed a distinct disease-specific profile. Integrating both secretome analyses, we identified EMILIN1, an ECM glycoprotein not previously studied in skeletal muscle, as a robust shared candidate; EMILIN1 is enriched in the DMD secretome, further upregulated by TGFβ, and downregulated upon SETDB1 depletion. We confirmed EMILIN1 overexpression in DMD patient muscle biopsies, validating its pathological relevance. Functionally, EMILIN1 depletion modulated myogenic differentiation and reduced expression of the fibrotic marker SERPINE1. These findings establish EMILIN1 as a novel secreted regulator of myogenesis and fibrosis, and implicate SETDB1 in shaping the TGFβ-dependent secretome in DMD. Our integrative proteomic approach provides new insights into the molecular drivers of impaired regeneration in DMD and highlights potential therapeutic targets. - Source: PubMed
Publication date: 2026/05/09
Zamperoni MaevaMuraine LauraTran Minh-YGranados AliceBigot AnnePetit ValentinBensalah MonaOhana JessicaLegros VéroniqueBoyarchuk EkaterinaBruce JohannaChevreux GuillaumeJoliot VéroniqueNegroni ElisaMoulin MarylineTrollet CapucineAit-Si-Ali Slimane - Ovarian cancer (OV) is one of the deadliest gynecological malignancies, and its high heterogeneity significantly impacts treatment efficacy. Against this background, the molecular mechanisms underlying the pathogenesis of this lethal disease have attracted extensive research attention. However, the pathogenic mechanisms of OV remain incompletely understood. Therefore, this study systematically investigates the pathogenesis of OV. This study collected 20 paired clinical samples comprising OV tissues and benign ovarian tissues to investigate RASSF2 expression. The biological effects of RASSF2 were investigated using both in vitro and in vivo models, including assessments of proliferation and migration. The impact of RASSF2 on PTEN protein stability was examined through co-immunoprecipitation and cycloheximide (CHX) chase assays. Additionally, chromatin immunoprecipitation (ChIP) was performed to investigate the SETDB1/RASSF2 interaction and H3K9me3 modifications on the chromatin of RASSF2. OV tissues exhibited significantly lower RASSF2 expression compared to normal tissues, and this reduction was associated with poorer patient survival. Overexpression of RASSF2 inhibited the proliferation and migration of OV cells. Additionally, RASSF2 inhibited OV growth in vivo. Mechanistically, RASSF2 stabilized PTEN expression to inhibit the activation of PI3K/AKT pathway. In addition, SETDB1 drove OV progression by increasing H3K9me3 enrichment at the RASSF2 promoter to negatively regulate RASSF2 expression. H3K9me3‑modified RASSF2 promotes ovarian cancer metastasis by regulating PTEN expression, which may offer a potential therapeutic target to counteract distant dissemination of OV. - Source: PubMed
Publication date: 2026/05/07
Wang JingLi XinyuChang JianmiaoHou XiaoxueSun LijiaYan YananShu LishaWu Xin