更新于：2024-05-01

CIART

circadian associated repressor of transcription

更新于：2024-05-01

基本信息

别名

BC017397、C1orf51、ChIP-derived repressor of network oscillator

+ [5]

简介

Transcriptional repressor which forms a negative regulatory component of the circadian clock and acts independently of the circadian transcriptional repressors: CRY1, CRY2 and BHLHE41. In a histone deacetylase-dependent manner represses the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Abrogates the interaction of BMAL1 with the transcriptional coactivator CREBBP and can repress the histone acetyl-transferase activity of the CLOCK-BMAL1 heterodimer, reducing histone acetylation of its target genes. Rhythmically binds the E-box elements (5'-CACGTG-3') on circadian gene promoters and its occupancy shows circadian oscillation antiphasic to BMAL1. Interacts with the glucocorticoid receptor (NR3C1) and contributes to the repressive function in the glucocorticoid response (By similarity).

关联

100 项与 CIART 相关的临床结果

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100 项与 CIART 相关的转化医学

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0 项与 CIART 相关的专利（医药）

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项与 CIART 相关的文献（医药）

2023-12-25·Current issues in molecular biology

Comparative Transcriptome Analyses Provide New Insights into the Evolution of Divergent Thermal Resistance in Two Eel Gobies.

Article

作者: Jing Liu ; Tianwei Liu ; Yantao Liu ; Yuzhen Wang ; Liqin Liu ; Li Gong ; Bingjian Liu ; Zhenming Lü

Adaptation to thermal conditions in tidal mudflats always involves tolerating frequent fluctuations and often extreme environmental temperatures. Regulation of gene expression plays a fundamental role in the evolution of these thermal adaptations. To identify the key gene regulatory networks associated with the thermal adaptation, we investigated the capability of cold tolerance, as well as the transcriptomic changes under cold stress in two mudflat inhabitants (Odontamblyopus lacepedii and O. rebecca) with contrasting latitude affinity. Our results revealed a remarkable divergent capacity of cold tolerance (CT_min: 0.61 °C vs. 9.57 °C) between the two gobies. Analysis of transcriptomic changes under cold stress unveiled 193 differentially expressed genes exhibiting similar expression profiles across all tissues and species, including several classic metabolic and circadian rhythm molecules such as ACOD and CIART that may represent the core cold response machinery in eel gobies. Meanwhile, some genes show a unique expression spectrum in the more cold-tolerant O. lacepedii suggesting their roles in the enhanced cold tolerance and hence the extreme thermal adaptations. In addition, a weighted gene co-expression network analysis (WGCNA) revealed a subset of metabolic hub genes including MYH11 and LIPT2 showing distinct down-regulation in O. lacepedii when exposed to cold stress which highlights the role of reduced energy consumption in the enhanced cold tolerance of eel gobies. These findings not only provide new insights into how mudflat teleosts could cope with cold stress and their potential evolutionary strategies for adapting to their thermal environment, but also have important implications for sound management and conservation of their fishery resources in a scenario of global climate warming in the marine realm.

2023-09-30·Journal of neuroinflammation

Unbiased multitissue transcriptomic analysis reveals complex neuroendocrine regulatory networks mediated by spinal cord injury-induced immunodeficiency.

Article

作者: Hong Zeng ; Li Cheng ; De-Zhi Lu ; Shuai Fan ; Ke-Xin Wang ; Li-Li Xu ; Bin Cai ; Mou-Wang Zhou ; Jin-Wu Wang

BACKGROUND:

Spinal cord injury (SCI), which causes loss of sensory and motor function in the body below the level of injury, is a devastating disease of the central nervous system. SCI leads to severe secondary immunosuppression, called SCI-induced immunodeficiency syndrome (SCI-IDS), which is characterized by increased susceptibility to infection and further exacerbates neurological dysfunction. Several studies have suggested that SCI-IDS is an independent risk factor for poor neurological prognosis. SCI-IDS predominantly occurs following injury above the T5 levels and eventually leads to systemic immune failure, possibly via the sympathetic-adrenal medullary axis and the hypothalamic‒pituitary‒adrenal (HPA) axis. However, the mechanism remains unclear.

METHODS AND OBJECTIVES:

The concentrations of adrenocorticotropic hormone and cortisol in plasma, as well as changes in sympathetic activity (blood pressure and catecholamine levels in plasma), were assessed in rats in the high-level (T3) spinal cord injury (T3-SCI) group and the low-level (T10) spinal cord injury (T10-SCI) group. Second, the differential regulation of the gene network between the sympathetic-adrenal medullary axis and the HPA axis was explored by histology and multitissue transcriptomics, and the neuroendocrine-immune network associated with SCI-IDS was further elucidated.

RESULTS:

The spleen and thymus gland, which are secondary immune organs, were significantly atrophied in rats in the T3-SCI group, and the white pulp of the spleen was significantly atrophied. The level of cortisol, which is mediated by the adrenal glands, was markedly elevated, but norepinephrine levels were markedly decreased. There was no difference in adrenocorticotropic hormone expression between any of the groups. The transcriptome analysis results showed that the downregulated differentially expressed genes (DEGs) in the T3-SCI group were enriched in the GO term immunoregulation, indicating that splenic immune function was markedly impaired after high-level SCI. The upregulated DEGs in the hypothalamus (hub genes: Nod2, Serpine1, Cebpb, Nfkbil1, Ripk2, Zfp36, Traf6, Akap8, Gfer, Cxcl10, Tnfaip3, Icam1, Fcgr2b, Ager, Dusp10, and Mapkapk2) were significantly enriched in inflammatory pathways, and the downregulated genes (hub genes: Grm4, Nmu, P2ry12, rt1-bb1, Oprm1, Zfhx2, Gpr83, and Chrm2) were enriched in pathways related to inhibitory Gi-mediated G protein-coupled receptor (Gi-GPCR) neurons and neuropeptide changes. The upregulated genes in the adrenal glands (hub genes: Ciart, per2, per3, cry1, and cry2) were enriched in cortisol secretion and circadian rhythm changes, and the downregulated genes (hub genes: IL7r, rt1-bb, rt1-bb1, rt1-da, rt1-ba, cd74, cxcr3, vcam1, ccl5, bin1, and IL8) were significantly enriched in MHC-mediated immune responses.

CONCLUSIONS:

To explore the possible mechanism underlying SCI-IDS, this study assessed the differential regulation of the gene network associated with neuroendocrine immunity after SCI. Progressive neuroinflammation spreads after injury, and neurotransmission through Gi-mediated G protein-coupled receptors in the HPA axis and neuropeptide production by the hypothalamus are inhibited. Disruption of the connection between the hypothalamus and the adrenal glands causes autonomous regulation of the adrenal glands, disturbance of circadian rhythm and finally hypercortisolemia, leading to general suppression of peripheral adaptive immunity. Neuraxial nerve inflammation caused by SCI persists indefinitely, blocking nerve repair; persistent system-wide immunosuppression in the periphery results in increased susceptibility to infection, leading to poor neurological prognosis.

2023-04-13·Life sciences

Aerobic exercise reduced the amount of CHRONO bound to BMAL1 and ameliorated glucose metabolic dysfunction in skeletal muscle of high-fat diet-fed mice.

Article

作者: Lei Xu ; Jie Jia ; Shudan Miao ; Lijing Gong ; Jin Wang ; Shiyi He ; Ying Zhang

AIMS:

The purpose of this study was to investigate the effects of aerobic exercise on the CHRONO-BMAL1 pathway and glucose metabolism in skeletal muscle of high-fat diet (HFD)-fed mice.

MAIN METHODS:

Male C57BL/6J mice were randomly allocated into four groups: normal chow diet with control (NCD + CON), NCD with exercise (NCD + EXE), HFD with control (HFD + CON) and HFD with exercise (HFD + EXE). The NCD and HFD groups were respectively fed a diet of 10 % and 60 % kilocalories from fat for 12 weeks. During the dietary intervention, EXE groups were subjected to 70 % VO_2max intensity of treadmill exercise six times per week for 12 weeks. Body weight, energy intake, fat weight, serum lipid profiles, systemic glucose homeostasis, the amount of CHRONO bound to BMAL1, the enzymatic activity, mRNA and protein expression involved in glucose metabolism of skeletal muscle were measured.

KEY FINDINGS:

The results showed that the 12-week HFD feeding without exercise induced weight gain, serum dyslipidemia and insulin resistance. Furthermore, HFD increased the amount of CHRONO bound to BMAL1 and repressed the glucose metabolism in skeletal muscle. However, aerobic exercise prevented weight gain, serum dyslipidemia and systemic insulin resistance in the HFD-fed mice. Meanwhile, aerobic exercise also decreased the amount of CHRONO bound to BMAL1 and increased the glucose uptake, glucose oxidation and glycogenesis in skeletal muscle of the HFD-fed mice.

SIGNIFICANCE:

These data suggested that aerobic exercise could counterbalance CHRONO interacted with BMAL1 and prevent glucose metabolism dysfunction of skeletal muscle, and finally maintain whole-body insulin sensitivity in the HFD-fed mice.

项与 CIART 相关的新闻（医药）

2023-03-15

·生物谷

Nat Cell Biol | 陈水冰团队利用类器官揭示CIART/NR4A1/RXR信号通路在调控新冠病毒感染中的重要作用

截至目前，新冠病毒大流行在全球范围造成了超过七亿六千万感染病例，其中死亡病例超过六百八十万。新冠病毒不仅感染呼吸系统，还可以感染人体多种其他组织，包括肝脏，胰腺，肾脏，大脑，肠道，心脏等等。近年来，人多能干细胞来源的类器官作为一种新兴的模型系统被广泛用于研究疾病发生和组织器官发育。在之前的研究中，类器官被用于研究新冠病毒的易感性，病毒与宿主细胞相互作用，以及药物筛选等。然而，调控新冠病毒感染的机理并没有完全阐明，能不能通过在不同组织中靶向共同的因子抑制新冠病毒感染也不清楚。2023年3月15日，康奈尔大学威尔医学院陈水冰团队在Nature Cell Biology发表了题为 A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection 的研究论文。研究人员利用人多能干细胞分化得到了可以被新冠病毒高效感染的心肌细胞，肺泡类器官，气管类器官。在此基础上，研究人员用不同剂量的新冠病毒感染了这些细胞/类器官，并通过RNA-seq系统分析了新冠病毒感染引起的转录组变化。过往的研究表明，新冠病毒可以通过上调某些宿主基因，比如ACE2的表达而进一步促进感染。本研究鉴定了18个在不同细胞/类器官中被新冠病毒感染后上调的宿主基因，进一步在心肌细胞中逐一敲除这些基因证实CIART，EGR1，FOS，H2AC6，H2BC5，JUN，MXD1，NR1D1，NR4A1，NR4A3，PPP1R15A，SOCS3，TIPARP影响新冠病毒感染，其中敲除CIART抑制感染效果最显著。研究人员进一步利用CRISPR/Cas9基因编辑在人多能干细胞中敲除CIART，并分化得到野生型和CIART敲除心肌细胞，肺泡类器官，气管类器官。与野生型对照相比，CIART敲除细胞/类器官抵抗新冠病毒感染能力显著增强。scRNA-seq显示气管类器官中的多种细胞类型，尤其是纤毛样细胞在CIART敲除后对新冠病毒更不易感。研究发现，不止新冠病毒，流感病毒感染同样可以上调CIART表达水平，提示CIART可能与多种病毒感染有关。之前的研究显示CIART基因编码调控昼夜节律的转录因子，研究人员进一步通过CUT&RUN在心肌细胞全基因组范围寻找受CIART调控的下游因子，结合CIART敲除和野生型心肌细胞的RNA-seq，ATAC-seq数据，研究人员发现CIART可以结合在NR4A1的启动子区域，影响NR4A1基因序列的染色质可及性。在心肌细胞中敲除CIART，可以下调NR4A1表达水平。这些结果表明NR4A1是受CIART调控的下游因子。有意思的是，NR4A1是在之前筛选中鉴定的影响新冠病毒感染的候选基因。功能实验证实敲除NR4A1也可以使心肌细胞，肺泡类器官，气管类器官对新冠病毒的易感性降低。对RNA-seq数据进行信号通路富集分析发现，CIART敲除在各种细胞/类器官中抑制了RXR通路。qPCR检测发现NR4A1敲除同样下调了RXR信号通路相关基因。进一步用RXR通路的小分子抑制剂HX531和PA452处理各种细胞/类器官，同样发现新冠病毒感染被显著抑制。由于RXR通路在调控脂肪酸代谢中发挥重要作用，而已有报道显示抑制脂肪酸合成可以有效抑制新冠病毒感染，研究人员分析RNA-seq数据，发现CIART敲除或者HX531处理下调了多个脂肪酸代谢相关基因；代谢组学分析进一步确认CIART敲除或者HX531处理下调了多种脂肪酸的合成。总的来说，本研究系统分析了新冠病毒感染对人多能干细胞来源的多种细胞/类器官在转录组水平的影响，鉴定到多个影响新冠病毒感染的宿主基因，并具体研究了CIART影响新冠病毒感染的机理，揭示了CIART/NR4A1/RXR信号通路在调控新冠病毒感染中的重要作用。原文链接：https://www-nature-com.libproxy1.nus.edu.sg/articles/s41556-023-01095-y会议推荐RECOMMENDATIONS点击了解详情会议信息大会时间：2023年5月19-20日大会地点：上海大会主题：前沿交叉创新融合扫描上方二维码或者点击【阅读原文】立即报名参会报名/媒体合作17321098232（微信同号）

基因疗法