更新于：2024-05-01

KMT5A

lysine methyltransferase 5A

更新于：2024-05-01

基本信息

别名

H4-K20-HMTase KMT5A、Histone-lysine N-methyltransferase KMT5A、KMT5A

+ [14]

简介

Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins (PubMed:12086618, PubMed:12121615, PubMed:15964846, PubMed:17707234, PubMed:27338793). Specifically monomethylates 'Lys-20' of histone H4 (H4K20me1) (PubMed:12086618, PubMed:12121615, PubMed:15964846, PubMed:27338793, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:16517599). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression (PubMed:12086618, PubMed:12121615, PubMed:15964846, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:16517599). Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes (PubMed:12086618, PubMed:12121615, PubMed:15964846, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:16517599). Required for cell proliferation, probably by contributing to the maintenance of proper higher-order structure of DNA during mitosis (PubMed:12086618, PubMed:12121615, PubMed:15964846, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:16517599). Involved in chromosome condensation and proper cytokinesis (PubMed:12086618, PubMed:12121615, PubMed:15964846, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:16517599). Nucleosomes are preferred as substrate compared to free histones (PubMed:12086618, PubMed:12121615, PubMed:15964846, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:16517599). Mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes (PubMed:17707234). Plays a negative role in TGF-beta response regulation and a positive role in cell migration (PubMed:23478445).

关联

100 项与 KMT5A 相关的临床结果

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100 项与 KMT5A 相关的转化医学

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0 项与 KMT5A 相关的专利（医药）

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324

项与 KMT5A 相关的文献（医药）

2024-02-01·Aging

Interaction of Sp1 and Setd8 promotes vascular smooth muscle cells apoptosis by activating Mark4 in vascular calcification.

Article

作者: Yun Li ; Meijuan Cheng ; Jingjing Jin ; Dongxue Zhang ; Shenglei Zhang ; Yaling Bai ; Jinsheng Xu

Vascular calcification (VC) is directly related to high mortality in chronic kidney disease (CKD), and cellular apoptosis of vascular smooth muscle cells (VSMCs) is a crucial process in the initiation of VC. Microtubule affinity-regulating kinase 4 (Mark4), known as a serine/threonine protein kinase, can induce cell apoptosis and autophagy by modulating Akt phosphorylation. However, the potential functions and molecular mechanisms of Mark4 in VSMCs apoptosis and calcification need to be further explored. Initially, our data indicated that the mRNA expression of Mark4 was prominently elevated in high phosphorus-stimulated human VSMCs compared with the other members in Marks. Consistently, Mark4 expression was found to be significantly increased in the calcified arteries of both CKD patients and rats. In vitro, silencing Mark4 suppressed apoptosis-specific marker expression by promoting Akt phosphorylation, finally attenuating VSMCs calcification induced by high phosphate. Mechanically, the transcription factor Sp1 was enriched in the Mark4 promoter region and modulated Mark4 transcription. Moreover, SET domain-containing protein 8 (Setd8) was proved to interact with Sp1 and jointly participated in the transcriptional regulation of Mark4. Finally, rescue experiments revealed that Setd8 contributed to VSMCs apoptosis and calcification by modulating Mark4 expression. In conclusion, these findings reveal that Mark4 is transcriptionally activated by Sp1, which is interacted with Setd8, to promote VSMCs calcification through Akt-mediated antiapoptotic effects, suggesting that Mark4 represents a potent and promising therapeutic target for VC in CKD.

2024-01-05·Insects

Alterations in Histone Methylation States Increased Profusion of Lethal(2)-Essential-for-Life-Like (l(2)elf), Trithorax and Polycomb Genes in Apis mellifera under Heat Stress.

Article

作者: Ahmad A Alghamdi ; Yehya Z Alattal

Histone post-translational modifications (PTMs) represent a key mechanism in the thermal adaptation of the honeybee Apis mellifera. In this study, a chromatin immunoprecipitation assay and qPCR were employed to explore the changes in the methylation states of H3K4m2, H3K4m3, H3K27m2 and H3K27m3 associated with l2efl (ID: 72474, 724405, 724488), histone methyltransferases (HMTs) ((trx) and PR-set7) and Polycomb (Pc) and (Su(z)12) genes in A. m. jemenitica (tolerant subspecies) and A. m. carnica (susceptible subspecies) in response to heat treatment (42 °C for 1 h). The results revealed significant enrichment fold changes in the methylation/demethylation of most H3K4 and H3K27 marks at all targeted genes. These changes increased the profusion of l2efl (ID: 72474, 724405, 724488), histone methyltransferases (HMTs) (trx) and Polycomb (Pc) and Su(z)12 and decreased the profusion of HMT (PR-set7) in both honeybee subspecies. The changes in the methylation enrichment folds of histone methyltransferases (HMTs) ((trx), PR-set) and Polycomb (Pc), Su(z)12 genes demonstrate the well-harmonized coordination of epigenetic gene regulation in response to heat treatment. Compared to the control, the changes in the methylation enrichment folds of H3K4m3 at Polycomb Su(z)12 were about 30× and 100× higher in treated A. m. jemenitica and A.m. carnica, respectively. Similarly, changes in the methylation/demethylation enrichment folds of HMT (trx) and Polycomb (Pc) and Su(z)12 were 2-3× higher in A. m. carnica than in A. m. jemenitica after treatment (42 °C). It is evident that post-translational chromatin modification in both honeybee subspecies can diminish heat stress impact by (I) increasing the transcriptional provision of l2efl associated with survival and (II) increasing the silencing of genes associated with general cellular activities.

2024-01-01·Life science alliance

DCAF14 regulates CDT2 to promote SET8-dependent replication fork protection.

Article

作者: Neysha Tirado-Class ; Caitlin Hathaway ; Anthony Nelligan ; Thuan Nguyen ; Huzefa Dungrawala

DDB1- and CUL4-associated factors (DCAFs) CDT2 and DCAF14 are substrate receptors for Cullin4-RING E3 ubiquitin ligase (CRL4) complexes. CDT2 is responsible for PCNA-coupled proteolysis of substrates CDT1, p21, and SET8 during S-phase of cell cycle. DCAF14 functions at stalled replication forks to promote genome stability, but the mechanism is unknown. We find that DCAF14 mediates replication fork protection by regulating CRL4^CDT2 activity. Absence of DCAF14 causes increased proteasomal degradation of CDT2 substrates. When forks are challenged with replication stress, increased CDT2 function causes stalled fork collapse and impairs fork recovery in DCAF14-deficient conditions. We further show that stalled fork protection is dependent on CDT2 substrate SET8 and does not involve p21 and CDT1. Like DCAF14, SET8 blocks nuclease-mediated digestion of nascent DNA at remodeled replication forks. Thus, unregulated CDT2-mediated turnover of SET8 triggers nascent strand degradation when DCAF14 is absent. We propose that DCAF14 controls CDT2 activity at stalled replication forks to facilitate SET8 function in safeguarding genomic integrity.

项与 KMT5A 相关的新闻（医药）

2023-12-24

·生物探索

EHJ | 复旦大学葛均波/翁鑫宇发现心肌梗死驱动单核细胞的训练免疫，加速动脉粥样硬化

尽管先进的医学治疗，急性冠状动脉综合征的幸存者仍面临着动脉粥样硬化相关血管事件复发的高风险，其根本原因尚不清楚。2023年12月12日，复旦大学葛均波及翁鑫宇共同通讯（第一作者董正）在European Heart Journal（IF=39）在线发表题为“Myocardial infarction drives trained immunity of monocytes, accelerating atherosclerosis”的研究论文，该研究证明心肌梗死驱动单核细胞的训练免疫（trained immunity），加速动脉粥样硬化。在MI和IR小鼠中，暴露于HFD或氧化低密度脂蛋白(oxLDL)刺激后，血液单核细胞和骨髓源性巨噬细胞表现出脾脏酪氨酸激酶(SYK)、赖氨酸甲基转移酶5A (KMT5A)和CCHC型锌指核酸结合蛋白(CNBP)表达升高。MI诱导的训练免疫可通过骨髓移植传播，加速初代受者的动脉粥样硬化。KMT5A特异性地将组蛋白H4的Lys20单甲基化(H4K20me)募集到SYK的基因体上，并与CNBP协同反激活SYK。体内小干扰RNA (siRNA)抑制KMT5A或CNBP可能减缓心肌梗死后动脉粥样硬化。6-羟多巴胺去交感神经能减少心肌梗死后动脉粥样硬化和炎症。ST段抬高型心肌梗死(STEMI)晚期冠状动脉病变患者的经典单核细胞表达更高的SYK和KMT5A基因水平。这些发现强调了单核细胞训练免疫在心肌梗死后加速动脉粥样硬化中的关键作用，这意味着血液经典单核细胞中的SYK可能是STEMI患者动脉粥样硬化进展的预测因素。尽管由于心血管医学技术的进步，越来越多的急性心肌梗死(MI)患者得到了及时有效的治疗，但心肌梗死后动脉粥样硬化相关血管事件复发的高风险仍持续多年。先前的研究已经证实，在心肌梗死、下肢缺血或中风等缺血事件后，动脉狭窄伴动脉粥样硬化作为潜在病理过程的发生率显著增加。动脉粥样硬化是一种以脂质和免疫细胞在血管内膜逐渐积聚，导致动脉粥样硬化形成为特征的病理过程在这个过程中，单核细胞和巨噬细胞在浸润到动脉病变后起着至关重要的作用。目前的临床研究也表明，调节单核细胞的表型可以减轻动脉粥样硬化及其临床并发症在小鼠中，心肌梗死通过刺激骨髓(BM)肾上腺素能受体加速动脉粥样硬化的进展，从而驱动单核细胞进入循环，进而促进动脉粥样硬化的发生。虽然单核细胞的循环寿命约为一周，但心肌梗死后动脉粥样硬化复发的风险可持续数年甚至数十年，其中的机制尚不完全清楚。最近，有研究表明，先天免疫细胞保留了先前暴露于微生物或炎症损伤的记忆，使它们能够对未来遇到相同或不相关的刺激产生更强的反应。这种被称为“训练免疫”的现象受到表观遗传机制和代谢重编程的强烈调节，这可能导致先天免疫细胞持久的促炎表型。在病理条件下，慢性炎症性疾病可以通过训练免疫增加对另一种炎症引发疾病的易感性。例如，来自牙周炎患者或实验性牙周炎模型小鼠的单核细胞受到适应性不良的脑卒中介导的免疫过程的训练，从而促进骨关节炎的发生。机理模式图（图源自European Heart Journal ）经过训练的免疫力也会促进动脉粥样硬化的发生和发展先前的研究表明，抗炎疗法可以降低复发性心血管事件。该发现缺血后小鼠经历了明显的免疫训练，激活全身炎症，并通过赖氨酸甲基转移酶5A (KMT5A)和cchc型锌指核酸结合蛋白(CNBP)在单核细胞中增加SYK(脾酪氨酸激酶)的表达。这些发现在从人外周血中提取的经典单核细胞中得到进一步验证。该研究证实单核细胞的免疫训练加速心肌梗死后动脉粥样硬化，单核细胞中的SYK可能是预防心肌梗死后动脉粥样硬化进展的分子靶点。参考文献：Dong Z, Hou L, Luo W, Pan LH,et al. Myocardial infarction drives trained immunity of monocytes, accelerating atherosclerosis. Eur Heart J. 2023 Dec 12:ehad787. doi: 10.1093/eurheartj/ehad787. Epub ahead of print. PMID: 38085922.文章来源：“iNature”责编|探索君排版|探索君End往期精选围观王晓红教授团队：绘制单次冷冻囊胚移植成功的女性植入期外周血microRNA动态表达谱，开拓领域创新研究热文维生素B12在细胞重编程与组织再生中发挥关键作用！热文不孕症治疗新方向！又一导致女性不孕的关键因素被发现热文Let-7家族miRNA或为癌症潜在免疫治疗靶点热文一项最新发现或可用于阿尔茨海默病药物开发点击“阅读原文”，了解更多~

siRNA临床研究