Ask about this productRelated genes to: ARNTL antibody
- Gene:
- ARNTL NIH gene
- Name:
- aryl hydrocarbon receptor nuclear translocator like
- Previous symbol:
- -
- Synonyms:
- MOP3, JAP3, BMAL1, PASD3, bHLHe5
- Chromosome:
- 11p15.3
- Locus Type:
- gene with protein product
- Date approved:
- 1997-11-06
- Date modifiied:
- 2017-08-18
Related products to: ARNTL antibody
Related articles to: ARNTL antibody
- The mechanisms by which core clock components are spatially organized to ensure robust oscillations in mammals remain unclear. Here, we identify the positive limb factor BMAL1 as a phase-separating protein that forms dynamic biomolecular condensates essential for circadian transcription and behavior. Endogenous BMAL1 forms nuclear puncta that oscillate in sync with the circadian cycle. Deletion analysis and optogenetic clustering identify an N-terminal 90-amino acid intrinsically disordered region whose phosphorylation state tunes BMAL1 phase separation. Besides, BMAL1 condensates behave as multi-molecular assemblies that selectively recruit CLOCK, p300, MED1, and are specifically promoted by E-box DNA. Functionally, an IDR-deleted BMAL1 mutant fails to rescue rhythmic transcription in Bmal1-KO cells and cannot restore locomotor rhythms when reintroduced into SCN-specific Bmal1‑KO mice. These findings establish BMAL1 condensates as dynamic transcriptional hubs that couple phase separation to circadian rhythm in cells and in vivo. - Source: PubMed
Publication date: 2026/05/01
Gao WenzhenZhu LiWei YaliLuo GuowenWang JiaheWang LijiePeng ZhengyingLi XuanWu ZhuoxuanLi JingyiWu YanfenWang XiaoxiaoJing JunjunZou ShujuanZhao QingFan YiYuan QuanZhou Chenchen - Lung cancer, the leading cause of cancer-related mortality, faces significant therapeutic challenges due to chemoresistance. While metabolic reprogramming and circadian disruptions are implicated in tumor progression, their interplay in driving resistance remains unclear. This study identifies BMAL1, a core circadian regulator, as a key driver and potential initiator of cisplatin resistance in non-small cell lung cancer (NSCLC) through metabolic and oxidative stress pathways. We demonstrate that BMAL1 upregulates multidrug resistance protein MRP1 via HIF-1α-driven glycolysis, amplifying lactate production. Lactate activates the TAZ/c-Jun/Snail complex to increase MRP1 expression, establishing a feedforward loop that sustains chemoresistance. Furthermore, cisplatin and etoposide induce BMAL1 expression through AKT signaling in response to oxidative stress, creating a self-reinforcing resistance mechanism. Critically, targeting AKT or MRP1 reverses BMAL1-mediated resistance. These findings reveal BMAL1 as a metabolic orchestrator linking circadian dysfunction to chemoresistance and propose actionable strategies-such as AKT inhibition or chronotherapy-to circumvent therapeutic failure. This work underscores the necessity of targeting circadian-metabolic crosstalk to improve outcomes in NSCLC. - Source: PubMed
Shi ZixinQin ZiniuChen ChuantaoYang XiaolinHu YunhanMeng XiaohuiCao YuxiangTao XiangZhang ZhijianXie TianchengWei HuijunWu Zhihao - Bisphenol A (BPA) is a widely existing endocrine-disrupting chemical that poses potential threats to human and animal health, including inducing metabolic disorders. Although previous studies have reported the adverse effects of BPA on liver glucose and lipid metabolism, the underlying molecular mechanisms remain incompletely elucidated. This study systematically evaluated the effects of BPA exposure on liver glucose and lipid metabolism in mouse hepatocytes (AML12) and mouse models, and detected its association with circadian clock disruption. In vitro models, BPA exposure for 24 h significantly decreased the mRNA and protein expression levels of BMAL1 in AML12 cells, while significantly up-regulating the mRNA expression of Nr1d1 and Dbp. On the contrary, the expression of Nr1d1 and Dbp decreased significantly after 48 h of BPA exposure. It is worthy to note that both mRNA and protein levels of BMAL1 were significantly increased in forskolin synchronized AML12 cells. In addition, the genes related to glucose and lipid metabolism were also detected after BPA exposure. The results showed that BPA exposure significantly increased the expression of Cd36 and Glut2 in non-synchronized AML12 cells. Meanwhile, the elevation of Hmgcr expression and the reduction of Pparα were detected in forskolin synchronized AML12 cells. In vivo models, the results showed that ICR mice exposed to BPA (50 μg kg) for 42 consecutive days exhibited impaired glucose tolerance, decreased insulin sensitivity, increased liver glycogen storage, and decreased liver triglyceride (TG) levels. Meanwhile, the mRNA expression of Nr1d1 was significantly increased in mouse liver after BPA exposure. In addition, the mRNA expression of two lipid metabolism-related genes (Srebp1c and Elovl6) was significantly decreased in mouse liver after BPA treatment, but the expression level of Cd36 was significantly increased. In conclusion, this study demonstrates that BPA exposure impairs the circadian clock system and glucose and lipid metabolism in AML12 cells and mouse liver, providing important evidence that BPA overload in the environment can lead to the incidence of metabolic disorders in mammals. This study highlights the potential regulatory role of circadian clock system in BPA induced mammalian liver metabolic disorders and suggests that BPA may pose more profound potential risks to human and animal health. - Source: PubMed
Publication date: 2026/04/16
Dong HaoDing WenliXiao BonanLi CuimeiJiang HaizhenYang WanghaoLi DanLi ChaoZhang HaisenGao DengkeWang AihuaJin YapingChen Huatao - Accelerated cellular senescence may be a key process in the progression of periodontitis, as it integrates the devastating effects of the major risk factors for periodontitis. Circadian rhythm disruption (CRD) affects the expression levels of multiple genes, such as brain and muscle ARNT-Like-1 (BMAL1), which is thought to be an important trigger or exacerbator of periodontitis. Even though CRD mechanisms are acknowledged to control cellular senescence, their effect on the senescence that happens during periodontitis is not well defined. This research aimed to explore the role and pathogenic mechanism of CRD in periodontitis and the involvement of cellular senescence, with the purpose of providing innovative ideas for the prevention and treatment of periodontitis. A rat model combining CRD and periodontitis was established. Periodontal lesions were assessed via histological staining. The expression levels of core circadian genes and senescence markers were evaluated. Inflammatory mediators related to the senescence-associated secretory phenotype (SASP) were quantified. The BMAL1 agonist SR8278 was employed to verify the key role of BMAL1 and the BMAL1/cryptochrome 2 (CRY2)/period circadian regulator 1 (PER1) signaling pathway. Finally, the effect of BMAL1 modulation on cellular senescence was examined in lipopolysaccharide (LPS)-induced human periodontal ligament cells (hPDLCs). CRD exacerbated experimental periodontitis lesions and aggravated the periodontal tissue senescence phenotype. BMAL1/CRY2/PER1 gene levels were down-regulated in a model of CRD-complexed periodontitis, and restoration of BMAL1 levels could alleviate CRD-exacerbated periodontitis by attenuating the periodontal tissue senescence phenotype. Interestingly, LPS exposure resulted in increased cellular senescence and decreased BMAL1/CRY2/PER1 in hPDLCs. Knockdown of BMAL1 resulted in further upregulation of cellular senescence in hPDLCs, whereas overexpression of BMAL1 inhibited LPS-induced cellular senescence. This study establishes a significant link between CRD and the aggravation of experimental periodontitis, within which a dysregulated BMAL1/CRY2/PER1 axis and an enhanced senescence phenotype are prominent features. This perspective opens new avenues for periodontitis intervention by focusing on circadian rhythm modulation. - Source: PubMed
Publication date: 2026/04/16
Zheng ChaoHuiLi YuanYuanZhang YanLiGeng TaoZhou ZiLingJin BeiFangWang LuPing - Following extensive liver resections, diminished liver regeneration impairs the maintenance or restoration of sufficient functional liver mass. Currently, effective therapies to restore liver regeneration are lacking, rendering liver transplantation the sole treatment option for end-stage liver disease. Therefore, it is imperative to elucidate the regulatory mechanisms underlying liver regeneration. In this study, we employed a multi-omics approach integrating Hi-C, RNA-seq, and ATAC-seq to dissect the early regulatory mechanisms of liver regeneration in rats and mice. Our results indicate that immune and inflammatory processes are markedly enriched during the early phase of regeneration, accompanied by upregulation of glucocorticoids (GCs) and their receptor (GR). First, the expression dynamics of the GC-related circadian gene Nr1d1 and its regulatory network-including Nfκbiα, Arntl, Clock, and Rora-align with chromatin reorganization, leading us to propose that the GC-GR-Nr1d1 axis is involved in maintaining liver homeostasis. Second, the GR-regulated FoxO family is significantly enriched, and the FoxO-associated gene Klf2 exhibits coordinated changes in expression, chromatin accessibility, and chromatin structure. Functional experiments demonstrate that Klf2 negatively regulates hepatocyte proliferation. Hence, we propose the GC-GR-FoxOs-Klf2 axis acts as a checkpoint in hepatocyte proliferation, preventing premature activation of proliferation- and cell cycle-related genes and ensuring orderly and efficient liver regeneration. Our findings on the role of GCs in liver regeneration may further support their future therapeutic application in liver diseases such as liver fibrosis, alcoholic cirrhosis, and hepatocellular carcinoma (HCC). - Source: PubMed
Publication date: 2026/04/13
Ye BingyuXie DejianShen WenlongYue MeijuanJin QinpengGuo XinjieZhang YanLi PingZhao Zhihu