Ask about this productRelated genes to: SETD7 antibody
- Gene:
- SETD7 NIH gene
- Name:
- SET domain containing 7, histone lysine methyltransferase
- Previous symbol:
- -
- Synonyms:
- KIAA1717, SET7, SET7/9, Set9, KMT7
- Chromosome:
- 4q31.1
- Locus Type:
- gene with protein product
- Date approved:
- 2006-02-15
- Date modifiied:
- 2018-12-21
Related products to: SETD7 antibody
Related articles to: SETD7 antibody
- Hydroquinone (HQ), a major metabolite of benzene, is a recognized risk factor for acute myeloid leukemia (AML). However, the mechanisms underlying HQ-associated leukaemogenesis remain incompletely understood. Increasing evidence suggests that defective osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), contributes to HQ-induced hematopoietic dysfunction and leukemic progression. SET domain-containing 7 (SETD7) has been found to regulate the proliferation and differentiation of BMSCs, while autophagy is known to play a crucial role in promoting osteogenic differentiation. Therefore, this study aimed to investigate the regulatory roles of SETD7 and autophagy in the osteogenic differentiation of HQ-exposed BMSCs. The results demonstrated that HQ exposure was associated with decreased histone 3 lysine 4 monomethylation (H3K4me1) and SETD7 protein levels, autophagy, and osteogenic differentiation capacity in BMSCs. Activation of autophagy by rapamycin (Rapa) effectively rescued the BMSCs osteogenic differentiation reduced by HQ. Moreover, overexpression of SETD7 restored both autophagic activity and osteogenic differentiation capacity suppressed by HQ. Notably, co-treatment with the autophagy inhibitor 3-methyladenine (3-MA) abrogated the pro-osteogenic effects induced by SETD7 overexpression in HQ-exposed BMSCs. Collectively, these findings indicated that SETD7 promoted osteogenic differentiation in HQ-exposed BMSCs via autophagy-dependent mechanism. This study provides mechanistic insight into how HQ may disrupt the bone marrow microenvironment, highlights the role of SETD7 in maintaining osteogenic differentiation and autophagy in HQ-exposed BMSCs, and contributes to a better understanding of the epigenetic and cellular pathways involved in HQ-induced hematotoxicity. - Source: PubMed
Publication date: 2026/02/23
Shen YilinNiu YiboXu TaoLuo ZhilongSong DonghaoLuo ChihengLiu YanCui QilinChen DongxiaoZhao XinyuLuo HaoGao Yuting - Dynamic mechanical signaling of the extracellular matrix is a key determinant of mesenchymal stem cell (MSC) fate, closely regulating their proliferation, differentiation and migration. Previously, we developed a highly cell-adaptive dynamic hydrogel (HA-ADA) that modulates MSC fate through unknown mechanisms. Here, using human bone marrow-derived mesenchymal stem cells (hMSCs), we found that sustained mechanical stimulation provided by HA-ADA hydrogel induced rapid spreading and significantly enhanced their osteogenic differentiation while inhibiting adipogenesis. Mechanistically, miRNA sequencing revealed that this process was mediated by the downregulation of miR-376a-3p and miR-127-5p, thereby relieving their inhibitory effect on the methyltransferase SETD7. Elevated SETD7 expression catalyzed methylation of β-catenin and accelerated its nuclear translocation. In the nucleus, β-catenin further formed a transcriptional complex with YAP to synergistically amplify downstream signals and potently activate the expression of Runx2, a key transcription factor for osteogenesis, which ultimately drove osteogenic differentiation and inhibited adipogenesis. The present study elucidated a novel mechanism by which cell-adaptive hydrogels regulate the β-catenin/YAP signaling loop through the miR-376a-3p/miR-127-5p-SETD7 axis, thereby determining the osteogenic/adipogenic differentiation of stem cells, which not only deepens our understanding of mechanotransduction but also provides new targets and material design strategies for bone regeneration. - Source: PubMed
Publication date: 2026/02/11
Xie XudongHu LiangcongZhang YuemanMi BobinXu XiaoyueDing ChongLi YimingAl-Smadi FawwazChu XiangyuXiong YuanZhang KunyuBian LimingLiu Guohui - While suppression of the integrated stress response (ISR) has been shown to restore proteostasis and mitigate organ injury in various diseases, its role in acute liver failure (ALF) remains poorly defined. Here, we discovered that, during drug-induced ALF, hepatocytes exhibited early and transient activation of the eIF2α-ATF4 signaling pathway, whereas macrophages displayed delayed but sustained activation. Hepatocyte-specific deletion of ATF4 (ATF4) significantly protected mice from acetaminophen (APAP)-induced liver injury, whereas myeloid-specific ATF4 deletion (ATF4) increased susceptibility. Protection in ATF4 mice was associated with reduced hepatic necrosis, apoptosis, neutrophil infiltration, proinflammatory cytokine production, and serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels. Pharmacological inhibition of the ISR using ISR inhibitor (ISRIB) similarly ameliorated ALF, underscoring its therapeutic potential and the stage-dependent dual role of ISR signaling. Mechanistically, ATF4 in hepatocytes promoted mitochondrial dysfunction and inflammatory responses via the SETD7-NLRP3/interleukin-1β (IL-1β) axis. ATF4 transcriptionally upregulated SETD7, a non-histone methyltransferase that methylates NLRP3 at residues K192 and K684 within the NACHT (named after conserved sequences found in NAIP [neuronal apoptosis inhibitory protein], CIITA [MHC class II transactivator], HET-E [incompatibility locus protein from Podospora anserina], and TP1 [telomerase-associated protein 1]) and Leucine-Rich Repeat (LRR) domains, stabilizing NLRP3 and enhancing inflammasome activation. The biphasic role of ATF4 was further validated in a carbon tetrachloride (CCl)-induced acute liver injury model. These findings identify the ATF4-SETD7-NLRP3 axis as a key regulator of hepatic inflammasome homeostasis and suggest it as a promising therapeutic target for ALF treatment. - Source: PubMed
Publication date: 2026/02/16
Nie ZhentianLiu XiaohanZhang HongliChen ZhengyangSun XiaoyanLi YutingKong YaweiShu HongyanChen Wei - Family members of the SET domain family (SETD) of histone lysine methyltransferases (HKMTs) act as principal epigenetic regulators, modulating chromatin structure, transcription pathways, and immune responses. SETDs catalyze lysine methylation on histone and non-histone substrates, as well as non-histone proteins (e.g., p53, NF-κB). These biochemical modifications support gene activity requisite for directing immune cells, modulating cytokine cascades, and inflammatory responses. For SETD family members, systemic dysregulation has become the principal mechanistic fulcrum within the orchestration of major autoimmune and inflammatory syndromes, comprising rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), psoriasis, atherosclerosis and type 2 diabetes, and, to a lesser extent, multiple sclerosis (MS) and inflammatory bowel disease (IBD). SETD1A and SETD1B catalyze H3K4 methylation and regulate the chromatin states governing the proliferation of T-lymphocytes. SETD2 spatially regulates H3K36 trimethylation with the augmentation of DNA regulatory steps and cytokine signaling. SETD6 and SETD7, and other components, enhance the NF-κB signaling involving innate immune response and regulation of chromatin structure. Experimentally validated mutations transform transcript re-equilibration and catalysis of benign enzymes. These alterations disturb immune consistency and endorse predetermined inflammatory responses, and weaken self-tolerance. In the post-genomic era, integrated therapeutic approaches are emerging from potent SETD modulators, small inhibitors, epigenetic scissors, and multi-omics techniques. Overall, this review demonstrates the emerging domain of immuno-epigenetics, SETD enzymes, and the strategic value they could serve as therapeutic targets and biomarkers. - Source: PubMed
Publication date: 2026/01/23
Liu ChunhuiLin LeiYao GuoliangFan YonggangGuo Yongjun - Small extracellular vesicles (sEVs) including exosomes play an important role in intercellular communication and can exert immunomodulatory effects in recipient cells. We have shown that a single prophylactic intrathecal injection of sEVs from RAW 264.7 macrophages two weeks prior, promotes faster resolution of mechanical and thermal hypersensitivity in the complete Freund's adjuvant (CFA) mouse model of inflammatory pain. How this long-term memory develops, and how sEVs regulate immune responses are unknown. Recent studies have shown that priming microglia with inflammatory stimuli can enhance or suppress responses to a delayed secondary insult via epigenetic modifications. We hypothesized that prophylactic intrathecal administration of macrophage-derived sEVs confers accelerated resolution of inflammatory pain by reprogramming epigenetic memory in spinal microglia in recipient CFA model mice. To determine whether prophylactic sEVs could attenuate pain in the absence of microglia when administering sEVs, we ablated microglia using a colony-stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622. sEV-induced pain prophylaxis was completely abolished in PLX5622-fed mice, indicating that microglia are required to be present during sEV administration to confer early resolution of inflammatory pain hypersensitivity. ChIP-seq analysis in spinal microglia 14 days after sEV administration (prior to CFA) revealed an increased number of gene loci enriched for H3K4me1, a hallmark of innate immune memory. Furthermore, inhibiting the H3K4 mono-methyltransferase SETD7 abolished sEV-induced pain attenuation. Our findings indicate that both microglia and its epigenetic reprogramming contribute to pain prophylaxis induced by macrophage-derived sEVs, providing novel insights into the development of non-addictive preventive analgesia. - Source: PubMed
Publication date: 2026/01/16
Luo XuanWickman Jason RDaCunza Jason TTian YuzhenSacan AhmetAjit Seena K