更新于：2024-09-05

SMYD5

更新于：2024-09-05

基本信息

别名

[histone H4]-lysine20 N-trimethyltransferase SMYD5、Histone-lysine N-trimethyltransferase SMYD5、NN8-4AG

+ [8]

简介

Histone methyltransferase that specifically trimethylates 'Lys-20' of histone H4 to form trimethylated histone H4 lysine 20 (H4K20me3) which represents a specific tag for epigenetic transcriptional repression (By similarity). In association with the NCoR corepressor complex, is involved in the repression of toll-like receptor 4 (TLR4)-target inflammatory genes in macrophages by catalyzing the formation of H4K20me3 at the gene promoters (By similarity). Plays an important role in embryonic stem (ES) cell self-renewal and differentiation (By similarity). Promotes ES cell maintenance by silencing differentiation genes through deposition of H4K20me3 marks (By similarity). Maintains genome stability of ES cells during differentiation through regulation of heterochromatin formation and repression of endogenous repetitive DNA elements by depositing H4K20me3 marks (PubMed:28951459).

关联

100 项与 SMYD5 相关的临床结果

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100 项与 SMYD5 相关的转化医学

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0 项与 SMYD5 相关的专利（医药）

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项与 SMYD5 相关的文献（医药）

2024-01-11·Molecular psychiatry

Placental transcriptomic signatures of prenatal and preconceptional maternal stress.

Article

作者: Brennan H Baker ; Sophie Freije ; James W MacDonald ; Theo K Bammler ; Ciara Benson ; Kecia N Carroll ; Daniel A Enquobahrie ; Catherine J Karr ; Kaja Z LeWinn ; Qi Zhao ; Nicole R Bush ; Sheela Sathyanarayana ; Alison G Paquette

Prenatal exposure to maternal psychological stress is associated with increased risk for adverse birth and child health outcomes. Accumulating evidence suggests that preconceptional maternal stress may also be transmitted intergenerationally to negatively impact offspring. However, understanding of mechanisms linking these exposures to offspring outcomes, particularly those related to placenta, is limited. Using RNA sequencing, we identified placental transcriptomic signatures associated with maternal prenatal stressful life events (SLEs) and childhood traumatic events (CTEs) in 1 029 mother-child pairs in two birth cohorts from Washington state and Memphis, Tennessee. We evaluated individual gene-SLE/CTE associations and performed an ensemble of gene set enrichment analyses combing across 11 popular enrichment methods. Higher number of prenatal SLEs was significantly (FDR < 0.05) associated with increased expression of ADGRG6, a placental tissue-specific gene critical in placental remodeling, and decreased expression of RAB11FIP3, an endocytosis and endocytic recycling gene, and SMYD5, a histone methyltransferase. Prenatal SLEs and maternal CTEs were associated with gene sets related to several biological pathways, including upregulation of protein processing in the endoplasmic reticulum, protein secretion, and ubiquitin mediated proteolysis, and down regulation of ribosome, epithelial mesenchymal transition, DNA repair, MYC targets, and amino acid-related pathways. The directional associations in these pathways corroborate prior non-transcriptomic mechanistic studies of psychological stress and mental health disorders, and have previously been implicated in pregnancy complications and adverse birth outcomes. Accordingly, our findings suggest that maternal exposure to psychosocial stressors during pregnancy as well as the mother's childhood may disrupt placental function, which may ultimately contribute to adverse pregnancy, birth, and child health outcomes.

2023-11-04·STAR protocols

A flow cytometry-based assay to investigate HIV-1 expression in SMYD5 shRNA containing primary CD4⁺ T cells.

Article

作者: Daniela Boehm ; Melanie Ott

Delivering small hairpin RNAs (shRNAs) and the HIV-1 virus to primary CD4+ T cells with high transduction efficiency and high cell viability can be challenging. Here, we present a flow cytometry-based assay to knock down the host protein SMYD5 by shRNA and study the HIV-1 virus specifically in shRNA-containing cells. We describe steps for purifying CD4+ T cells, activating them with CD3/CD28 Dynabeads, transfection of plasmids into HEK293T cells, spinoculation with two different viruses, and analysis by flow cytometry. For complete details on the use and execution of this protocol, please refer to Boehm et al.¹.

2023-09-01·Current opinion in HIV and AIDS

HIV-1 transcriptional modulation: novel host factors and prospective therapeutic strategies.

Review

作者: Quentin M R Gibaut ; Luisa P Mori ; Susana T Valente

PURPOSE OF REVIEW:

This review highlights advances in HIV transcription and epigenetic latency mechanisms and outlines current therapeutic approaches to eliminate or block the HIV-1 latent reservoir.

RECENT FINDINGS:

Novel host factors have been reported to modulate HIV-1 transcription and latency. Chromatin affinity purification strategies followed by mass spectrometry (ChAP-MS) identified the chaperone protein p32 to play an important role in HIV-1 transcriptional regulation via interactions with the viral transcriptional activator Tat. Similarly, an shRNA screen identified the methyltransferase SMYD5 contributing to HIV-1 transcriptional activation also by modulating Tat activity. These new factors, among others, represent potential druggable targets that could be explored in the 'block-and-lock' or 'shock-and-kill' approaches.

SUMMARY:

The HIV-1 latent reservoir is established early after infection, persists during antiretroviral therapy, and is the source of viral rebound after treatment interruption. An HIV cure requires either eliminating this reservoir or blocking latent proviral reactivation in the absence of antiretroviral therapy (ART). Understanding the mechanisms and key-players modulating HIV transcriptional and reactivation may facilitate therapeutic advancements. Here we summarize, the latest findings on host factors' roles in HIV transcriptional regulation.

项与 SMYD5 相关的新闻（医药）

2023-09-09

·生物制品圈

厉害了！曹雪涛团队再发文

导读：在抗病毒先天应答中，IRF3的磷酸化对于诱导I型干扰素(IFN-I)的产生至关重要。9月6日，中国医学科学院北京协和医学院曹雪涛及Xu Xiaoqing在《Cell Death & Disease》上在线发表题为“Lysine methyltransferase SMYD2 inhibits antiviral innate immunity by promoting IRF3 dephosphorylation”的研究论文，该研究报道赖氨酸甲基转移酶SMYD2在病毒感染时抑制巨噬细胞中IFN-I和促炎细胞因子的表达。Smyd2缺陷小鼠通过产生更多的IFN-I和促炎细胞因子来抵抗病毒感染。https://www.nature.com/articles/s41419-023-06118-y#Abs1研究背景 01 先天免疫应答是保护宿主免受病原体感染的第一线。在先天免疫细胞和其他类型的细胞中表达的模式识别受体（PRR），例如RIG-I，MDA5和cGAS，可识别病原体相关分子模式（PAMP）以触发信号通路，例如MAVS-TBK1-IRF3途径，磷酸化IRF3（p-IRF3）易位到细胞核中，从而诱导I型干扰素（IFN-I）的产生，以消除包括病毒在内的入侵病原体。NF-κB对于感知病毒RNA或DNA后产生IFN-I和促炎细胞因子也至关重要。IRF3具有具有特征性5个色氨酸重复序列的N端DNA结合结构域（DBD），C端包含保守的IRF关联结构域（IAD）和磷酸受体位点丰富的序列。IRF3在细胞质中作为非活性单体组成型表达和定位，其由IAD两侧的自身抑制结构域维持。TBK1/IKKε对IRF3的磷酸化对于诱导IFN-I响应病毒感染至关重要，因此需要充分了解先天反应中IRF3磷酸化的调节。赖氨酸甲基转移酶通过甲基化修饰组蛋白和无组蛋白，甲基化通过调节染色质重塑和蛋白质构象在一系列生物学和免疫学过程中具有关键功能。SMYD蛋白是一类蛋白质赖氨酸甲基转移酶，其甲基化组蛋白和非组蛋白靶标，到目前为止有五个已鉴定的成员SMYD 1-5。SMYD是SMYD5的除外，它由s序列、MYND结构域、插入SET结构域（SETi）、ET、后ET和CTD结构域组成，并且该家族的结构很特殊，因为SET（杂散抑制因子、Zeste增强子、Trithorax）结构域由MYND结构域隔开。SET结构域是几乎所有组蛋白甲基转移酶中赖氨酸甲基化的保守催化单元，MYND结构域是锌指基序，主要介导蛋白质-蛋白质相互作用。据报道，SMYD蛋白在肿瘤发生、肌生成和心肌细胞分化中起重要作用。然而，SMYD2在抗病毒先天免疫应答中的功能尚不清楚。Smyd2的缺失促进一系列I型细胞因子和ISG的表达 02 转录组测序显示，与对照组相比，VSV感染的Smyd2−/− PM中有298个增加的基因和882个减少的基因（图4A，B）。KEGG分析表明，未受VSV刺激的Smyd2−/− PM的差异表达基因在泛素介导的蛋白水解、肌动蛋白细胞骨架调控、溶酶体、单纯疱疹感染、Rap1信号通路和趋化因子信号通路等信号通路中富集。VSV感染的Smyd2−/− PM的差异表达基因富集在TNF信号通路、PI3K-Akt信号通路、局灶粘附和ECM-受体相互作用等通路中。我们进一步分析了测序数据，以确认感染VSV的Smyd2−/− PM中参与免疫应答的基因表达增加。我们发现，与对照组相比，Smyd2−/− PM中一系列细胞因子（尤其是IFN-I）和转录因子Stat5a的mRNA表达显著增加（图4C）。此外，许多干扰素刺激的基因（ISG），如Bcl2l11和Trim家族，在Smyd2−/−PM中增加，以响应VSV感染（图4D）。几种ISG，如Ifit1，Isg15，Cxcl10和Ccl5，被证实在感染VSV的Smyd2−/− PM中显著增加（图4E）。综上所述，我们的转录组测序数据进一步证实，SMYD2通过靶向IFN-I产生来抑制抗病毒先天免疫应答。Smyd2缺陷巨噬细胞中抗病毒先天免疫应答增加。研究结论 03 本研究，我们证明了SMYD2通过抑制IRF3磷酸化来抑制抗病毒IFN-I的产生，IRF3磷酸化与其甲基转移酶活性无关。在机制上，SMYD2通过IRF3的结合IAD结构域与IRF3相互作用，磷酸酶PP1α被SMYD2募集到IRF3以减少IRF3的磷酸化。总体而言，SMYD2是先天反应中抗病毒干扰素的负调节因子。参考资料：https://www.nature.com/articles/s41419-023-06118-y#Abs1识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。