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自噬影响组蛋白修饰标记H3K4me3调控小鼠早期胚胎发育
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作者 胡静 朱伶 +2 位作者 谢娟 孔德营 刘豆豆 《中国组织工程研究》 北大核心 2026年第5期1147-1155,共9页
背景:自噬作为细胞发育的一个关键调控机制,在胚胎发育的不同阶段发挥着重要作用。目前对于胚胎中自噬如何通过组蛋白修饰来调控胚胎发育的机制尚不明确。目的:探究胚胎中自噬对H3K4me3修饰的影响以及对胚胎发育的影响。方法:将小鼠受... 背景:自噬作为细胞发育的一个关键调控机制,在胚胎发育的不同阶段发挥着重要作用。目前对于胚胎中自噬如何通过组蛋白修饰来调控胚胎发育的机制尚不明确。目的:探究胚胎中自噬对H3K4me3修饰的影响以及对胚胎发育的影响。方法:将小鼠受精卵分为对照组和自噬抑制剂处理组(磷酸氯喹处理组,3-甲基腺嘌呤处理组),分别体外培养至不同时期,分为早期2-细胞胚胎、中期2-细胞胚胎、晚期2-细胞胚胎、4-细胞胚胎、8-细胞胚胎、桑葚期胚胎、囊胚期胚胎。通过免疫荧光检测分析各组晚期2-细胞胚胎的活性氧、自噬标记蛋白LC3B、P62和DNA损失标记物γH2AX以及各阶段胚胎组蛋白H3K4me3的表达;通过染色体靶向切割和标签化(CUT&Tag)检测各组晚期2-细胞胚胎中H3K4me3修饰变化。结果与结论:①自噬抑制后,小鼠胚胎发育阻滞;②免疫荧光结果显示,自噬抑制后,与对照组相比,自噬抑制剂处理组的活性氧和γH2AX没有显著差异;③自噬抑制剂处理相对于对照组晚期2-细胞胚胎的H3K4me3水平显著升高;④CUT&Tag结果显示,自噬抑制后,H3K4me3在基因近端启动子区域富集显著增加,并且H3K4me3特异性结合基因增多;⑤结果表明,自噬可能通过调控H3K4me3修饰水平从而影响胚胎发育。 展开更多
关键词 小鼠 自噬 h3k4me3 胚胎发育 组蛋白修饰 活性氧 DNA损伤 小鼠胚胎 甲基化
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低温等离子体调节H3K4me2刺激灵芝生长和灵芝酸积累
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作者 张莹 黄青 《生物学杂志》 北大核心 2025年第3期1-8,共8页
研究从表观遗传学角度探讨纳秒脉冲介质阻挡放电等离子体(NS-DBD)刺激灵芝生长和灵芝酸生物合成机制。通过高效液相色谱法检测发现,NS-DBD可以促进灵芝酸的生物合成。生化指标检测发现,NS-DBD诱导了灵芝胞内活性氧的积累,使总超氧化物... 研究从表观遗传学角度探讨纳秒脉冲介质阻挡放电等离子体(NS-DBD)刺激灵芝生长和灵芝酸生物合成机制。通过高效液相色谱法检测发现,NS-DBD可以促进灵芝酸的生物合成。生化指标检测发现,NS-DBD诱导了灵芝胞内活性氧的积累,使总超氧化物歧化酶、过氧化氢酶、谷胱甘肽还原酶等抗氧化酶的活性升高。同时伴有灵芝酸生物合成相关基因转录水平的上调。免疫荧光和染色质免疫沉淀测序方法证实,NS-DBD处理后,灵芝酸合成通路上的基因hmgr、pmvk、mvd、sqs和ls的H3K4me2修饰水平都发生了显著变化。其中,基因hmgr、pmvk、mvd和ls的H3K4me2修饰主要分布于基因的外显子区域,而基因sqs的H3K4me2修饰则分布于上游2 kb和外显子区域。研究表明,NS-DBD通过刺激ROS积累调节灵芝酸合成通路上一些关键基因的H3K4me2修饰水平,进而调节灵芝的生长和灵芝酸的合成。 展开更多
关键词 低温等离子体 介质阻挡放电(DBD) 灵芝 灵芝酸 刺激效应 h3k4me2
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扰动流调控内皮细胞组蛋白去甲基化酶KDM5B和H3K4me3对颈动脉斑块形成的影响
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作者 吴丽丽 沈宇 《中国动脉硬化杂志》 2025年第2期117-124,共8页
[目的]探讨扰动流是否通过调控组蛋白去甲基化酶KDM5B和表观遗传修饰影响内皮细胞功能和动脉粥样硬化斑块形成。[方法]通过部分颈动脉结扎术(PCL),利用单细胞数据分析和免疫荧光染色观察扰动流作用下野生型小鼠颈动脉内皮细胞组蛋白甲... [目的]探讨扰动流是否通过调控组蛋白去甲基化酶KDM5B和表观遗传修饰影响内皮细胞功能和动脉粥样硬化斑块形成。[方法]通过部分颈动脉结扎术(PCL),利用单细胞数据分析和免疫荧光染色观察扰动流作用下野生型小鼠颈动脉内皮细胞组蛋白甲基化水平和组蛋白去甲基化酶的表达变化;利用qPCR和Western blot检测暴露于扰动流诱导的内皮细胞KDM5B和H3K4me3的表达;利用普通转录组测序分析KDM5B敲降对内皮细胞功能的影响;内皮细胞成环实验验证KDM5B对血管生成的影响;PCL结合高脂饲料喂食2周构建颈动脉斑块模型分析KDM5B敲降对斑块形成的影响。[结果]血管内皮细胞上存在大量H3K4me3甲基化修饰。扰动流使内皮细胞H3K4me3水平下降(P<0.01),并上调组蛋白去甲基化酶KDM5B表达(P<0.05)。与对照组相比,抑制KDM5B活性或敲降KDM5B表达后可以提高内皮细胞H3K4me3水平(P<0.05)。与Con313对照组相比,KDM5B敲降可以抑制内皮细胞血管生成,并使ApoE^(-/-)小鼠颈动脉斑块面积减少41.45%(Con313对照组:42.17%±1.90%,shKDM5B敲降组:24.69%±1.60%,P<0.01)。[结论]血液扰动流通过促进KDM5B表达,降低H3K4me3修饰,促进血管生成和动脉粥样硬化斑块形成,靶向KDM5B-H3K4me3轴可作为心血管疾病相关的候选治疗靶点。 展开更多
关键词 扰动流 h3k4me3 KDM5B 内皮细胞 颈动脉斑块形成
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鸡卵泡颗粒层组蛋白H3K4me3和H3K27me3的表达研究 被引量:1
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作者 李春苗 贾雪波 +3 位作者 王钱保 黄正洋 黄华云 赵振华 《安徽农业大学学报》 CAS CSCD 2023年第4期621-626,共6页
卵母细胞成熟过程受组蛋白H3K4me3(trimethylation of lysine 4 on histone 3)和H3K27me3(trimethylation of lysine 27 on histone 3)及其相关的甲基化和去甲基化酶的调控,因此考虑对鸡的卵泡发育也存在一定的影响。选取“苏禽3号”配... 卵母细胞成熟过程受组蛋白H3K4me3(trimethylation of lysine 4 on histone 3)和H3K27me3(trimethylation of lysine 27 on histone 3)及其相关的甲基化和去甲基化酶的调控,因此考虑对鸡的卵泡发育也存在一定的影响。选取“苏禽3号”配套系第一母本为研究对象,采用Western blot法探究组蛋白H3K4me3和H3K27me3在鸡卵泡不同发育阶段颗粒层中蛋白的表达模式。结果表明:在苏禽3号卵泡颗粒层中,组蛋白H3K4me3在卵泡发育不同阶段表达模式呈降低→升高→降低→升高的波浪形趋势,波浪变化较为平缓,在F5、F2和F13个表达高点的表达量与SWF(small white follicle)、LWF(large white follicle)、SYF(small yellow follicle)和F34个表达低点的表达差异显著(P<0.05)。组蛋白H3K27me3在不同发育阶段表达模式亦呈波浪形表达趋势,波浪变化起伏较明显,在SWF、SYF和F33个表达高点的表达量与F5、F4、F1和F24个表达低点的表达差异显著(P<0.05)。相关性分析显示,组蛋白H3K4me3与H3K27me3在不同发育阶段卵泡颗粒细胞中的表达呈较强的负线性相关(R=-0.808,P=0.000)。结果提示:组蛋白H3K4me3和H3K27me3在不同发育阶段卵泡颗粒层中的表达具有组织差异性,呈负相关的动态修饰性,可能共同协调卵泡生长过程中各基因的表达与功能,研究结果为鸡繁殖性状调控机理提供了理论依据。 展开更多
关键词 卵泡 颗粒细胞 组蛋白 h3k4me3 H3K27me3
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H3K4me3高表达与肝癌患者较差生存预后相关 被引量:2
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作者 伍刚 何传超 《现代肿瘤医学》 CAS 2018年第6期893-899,共7页
目的:探讨检测肝癌组织中组蛋白第三亚基四号赖氨酸的三甲基化(H3K4me3)蛋白的表达与肿瘤病理特点和肝癌患者生存预后的相关性。方法:免疫组化和Western-blot检测H3K4me3和组蛋白甲基转移酶(SET and MYND domain-containing protein 3,S... 目的:探讨检测肝癌组织中组蛋白第三亚基四号赖氨酸的三甲基化(H3K4me3)蛋白的表达与肿瘤病理特点和肝癌患者生存预后的相关性。方法:免疫组化和Western-blot检测H3K4me3和组蛋白甲基转移酶(SET and MYND domain-containing protein 3,SMYD3)在肝癌组织(n=168)和细胞株中的表达。此外,实验结果还在另外一个肝癌组织芯片(n=147)中进行验证。H3K4me3表达的最佳分界点(optimal cut-point)由X-tile程序确定,患者的预后由Kaplan-meier生存曲线描述。结果:H3K4me3高表达于肝癌细胞系和肝癌组织,其高表达与肝癌尤其是早期TNM1/2期患者的较差总体生存显著相关。单因素和多因素分析均提示H3K4me3表达水平是患者预后的独立危险因素。此外,H3K4me3和SMYD3在两组肝癌组织中均存在正相关表达。结论:H3K4me3表达水平能成为肝癌患者术后生存的预测因子,其高表达可能与SMYD3有关。 展开更多
关键词 肝细胞癌 h3k4me3 SMYD3 生存 预后
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H3K9ac、H3K4me2在卵巢浆液性上皮性肿瘤中的表达及意义 被引量:1
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作者 王蛟 杨清 毕芳芳 《现代肿瘤医学》 CAS 2014年第8期1917-1921,共5页
目的:探讨组蛋白H3第9位赖氨酸残基乙酰化(H3K9ac)及组蛋白H3第4位赖氨酸残基二甲基化(H3K4me2)在卵巢浆液性囊腺瘤、卵巢交界性浆液性囊腺瘤和卵巢浆液性囊腺癌组织中蛋白表达与浆液性上皮性卵巢癌发生、发展的关系及两者之间有无相关... 目的:探讨组蛋白H3第9位赖氨酸残基乙酰化(H3K9ac)及组蛋白H3第4位赖氨酸残基二甲基化(H3K4me2)在卵巢浆液性囊腺瘤、卵巢交界性浆液性囊腺瘤和卵巢浆液性囊腺癌组织中蛋白表达与浆液性上皮性卵巢癌发生、发展的关系及两者之间有无相关性。方法:应用免疫组织化学链霉菌抗生物素蛋白-过氧化酶连接法(SP法)检测H3K9ac、H3K4me2在30例卵巢浆液性囊腺瘤组织、30例卵巢交界性浆液性囊腺瘤组织及40例卵巢浆液性囊腺癌组织中的表达,观察表达差异并进行统计学处理。结果:H3K9ac在卵巢浆液性囊腺瘤组织中阳性表达率为93.33%,在卵巢交界性浆液性囊腺瘤组织中阳性表达率为66.67%,在卵巢浆液性囊腺癌中阳性表达率为42.50%,良性、交界性、恶性组织间两两比较差异有统计学意义(P<0.05)。在不同手术病理分期、不同组织学分级的卵巢浆液性囊腺癌组织中H3K9ac的阳性表达率有统计学差异(P<0.05)。H3K4me2在卵巢浆液性囊腺瘤组织中阳性表达率为90%,在交界性浆液性囊腺瘤组织中阳性表达率为73.33%,在卵巢浆液性囊腺癌中阳性表达率为52.50%,良性与交界性、交界性与恶性组织间比较差异无统计学意义(P>0.05),良性与恶性组织间比较差异有统计学意义(P<0.05)。在不同手术病理分期、不同组织学分级的卵巢浆液性囊腺癌组织中H3K4me2的阳性表达率无统计学差异(P>0.05)。H3K9ac、H3K4me2在卵巢浆液性囊腺癌组织中的表达呈正相关(r=0.732,P<0.001)。结论:H3K9ac、H3K4me2的低表达与浆液性上皮性卵巢癌的发生、发展有关,有可能成为浆液性上皮性卵巢癌诊断和治疗的新靶点。 展开更多
关键词 卵巢浆液性囊腺癌 H3K9ac h3k4me2 免疫组化
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组蛋白去甲基化酶KDM5A调控H3K4me3参与神经管畸形发生的分子机制 被引量:3
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作者 李建婷 解琪 +5 位作者 谷小龙 曹志华 彭志伟 赵虹 刘志贞 解军 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2024年第5期629-637,共9页
神经管畸形(NTDs)的病因与防治是出生缺陷领域研究的重点,叶酸可以预防神经管畸形但其机制不明。本文借助低叶酸细胞模型和低叶酸NTDs小鼠模型通过染色质免疫共沉淀、Cut&Tag等技术,探讨了组蛋白去甲基化酶lysine demethylase 5A(KD... 神经管畸形(NTDs)的病因与防治是出生缺陷领域研究的重点,叶酸可以预防神经管畸形但其机制不明。本文借助低叶酸细胞模型和低叶酸NTDs小鼠模型通过染色质免疫共沉淀、Cut&Tag等技术,探讨了组蛋白去甲基化酶lysine demethylase 5A(KDM5A)及其调控的下游组蛋白H3K4me3修饰在叶酸缺乏导致的NTDs发生中的潜在分子机制。结果显示,低叶酸的细胞模型中,qRT-PCR、Western印迹结果显示,KDM5A分子表达明显下降(P<0.05)。作为组蛋白H3K4me3调控的上游关键酶,进一步通过染色质免疫共沉淀ChIP、ChIP-qPCR实验证实,叶酸缺乏下组蛋白H3K4me3在神经发育基因Axin 2和Atoh 1基因启动子区富集增加(P<0.05)。通过构建KDM5A基因敲除细胞模型,借助Cut&Tag试验证实,KDM5A基因敲除后H3K4me3主要富集在神经发育基因上。最后在低叶酸导致的NTDs小鼠模型的脑组织中,RT-qPCR、Western印迹以及ChIP-qPCR实验显示,E9.5 d的NTDs胎鼠脑组织中KDM5A表达下降(P<0.05),Axin2、Atoh1表达升高(P<0.05),Axin2、Atoh 1基因启动子区的H3K4me3富集增多(P<0.05)。综上所述,KDM5A蛋白在叶酸缺乏导致的NTDs中发挥重要作用,其可通过调控下游H3K4me3进而调控神经发育靶基因Axin2、Atoh 1异常表达,介导NTDs的发生。本研究从叶酸缺乏介导KDM5A调控组蛋白修饰来探讨NTDs的发病机制,为降低出生缺陷,促进生殖健康提供依据。 展开更多
关键词 神经管畸形 叶酸 组蛋白去甲基化酶5A 组蛋白h3k4me3
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H3K4me3对猪卵母细胞体外成熟和早期胚胎发育的影响 被引量:2
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作者 曾毅仁 张彩玉 +2 位作者 侯晗琦 恽雪丹 李湘萍 《西南大学学报(自然科学版)》 CAS CSCD 北大核心 2021年第7期45-51,共7页
哺乳动物卵母细胞的成熟与组蛋白甲基化修饰密切相关.CPI-455是一种组蛋白去甲基化酶抑制剂,可特异性抑制组蛋白去甲基转移酶KDM5A/B的活性,提高H3K4me3(组蛋白H3第4位赖氨酸三甲基化)的表达水平.本实验在猪卵母细胞体外成熟过程中添加C... 哺乳动物卵母细胞的成熟与组蛋白甲基化修饰密切相关.CPI-455是一种组蛋白去甲基化酶抑制剂,可特异性抑制组蛋白去甲基转移酶KDM5A/B的活性,提高H3K4me3(组蛋白H3第4位赖氨酸三甲基化)的表达水平.本实验在猪卵母细胞体外成熟过程中添加CPI-455,探究H3K4me3组蛋白甲基化对猪卵母细胞体外成熟和早期胚胎发育的影响.首先,用不同浓度CPI-455在不同时间处理猪卵母细胞,发现在0~22 h添加5μmol CPI-455的处理方法效果最佳,卵母细胞成熟率与囊胚形成率均显著高于未处理组(p<0.05).0~22 h添加5μmol CPI-455处理卵母细胞显著提高了囊胚中H3K4me3的表达(p<0.05),降低了卵母细胞中KDM5A和KDM5B的表达(p<0.05),并且显著提高了囊胚中Nanog,Oct4,CDX2等多能性基因的表达(p<0.05).CPI-455处理可以通过降低卵母细胞中相关基因的表达,上调囊胚中多能性基因的表达,调控H3K4me3的甲基化水平,从而促进猪卵母细胞体外成熟和早期胚胎发育. 展开更多
关键词 卵母细胞 CPI-455 h3k4me3 体外成熟
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基于PARP-1/KDM5B/H3K4me3信号轴探讨温阳复元方含药血清对OGD/R诱导BV-2细胞损伤的保护机制
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作者 周珂青 张鼎 +3 位作者 孙春英 秦红玲 陈炜 胡跃强 《中药材》 北大核心 2024年第11期2852-2858,共7页
目的:基于PARP-1/KDM5B/H3K4me3信号轴探讨温阳复元方含药血清对OGD/R诱导BV-2细胞损伤的保护机制。方法:通过OGD/R诱导BV-2细胞,构建氧糖剥夺体外模型。CCK-8检测最佳干预浓度和时间点,Transwell观察各组细胞迁移,Hoechst 33342染色观... 目的:基于PARP-1/KDM5B/H3K4me3信号轴探讨温阳复元方含药血清对OGD/R诱导BV-2细胞损伤的保护机制。方法:通过OGD/R诱导BV-2细胞,构建氧糖剥夺体外模型。CCK-8检测最佳干预浓度和时间点,Transwell观察各组细胞迁移,Hoechst 33342染色观察细胞凋亡,免疫荧光化学法观察PARP-1、KDM5B蛋白表达,Western Blotting检测PARP-1、KDM5B、H3K4me3蛋白表达。结果:10%温阳复元方含药血清干预12 h细胞活力最高。与空白对照组比较,模型组细胞迁移能力显著减弱,凋亡显著增多,PARP-1、KDM5B蛋白表达显著升高,H3K4me3蛋白表达显著降低(P<0.05)。与模型组比较,Olaparib(PAPP-1抑制剂)组、温阳复元方含药血清组细胞迁移能力显著增强,凋亡显著减少,PARP-1、KDM5B蛋白表达显著降低,H3K4me3蛋白表达显著升高(P<0.05)。结论:温阳复元方可抑制PARP-1/KDM5B/H3K4me3信号轴的过度激活,减轻神经细胞损伤,发挥脑保护作用。 展开更多
关键词 温阳复元方 BV-2细胞 OGD/R PARP-1/KDM5B/h3k4me3信号轴 机制研究
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基于生物信息学方法和动物实验方法获取多房棘球蚴病组蛋白H3K4ME1的生物学功能和信号通路信息
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作者 朱鑫琳 陈佳昕 任利 《中国高原医学与生物学杂志》 CAS 2024年第2期124-130,共7页
目的基于生物信息学方法和动物实验方法获取多房棘球蚴病组蛋白H3K4ME1的生物学功能和信号通路信息。方法1.提取冻存组织细胞核。2.构建cut&tag文库。3.分析生物信息:1)评估多房棘球蚴病组蛋白H3K4ME1的测序数据;2)确定reads在基因... 目的基于生物信息学方法和动物实验方法获取多房棘球蚴病组蛋白H3K4ME1的生物学功能和信号通路信息。方法1.提取冻存组织细胞核。2.构建cut&tag文库。3.分析生物信息:1)评估多房棘球蚴病组蛋白H3K4ME1的测序数据;2)确定reads在基因组上的分布;3)分析单个样本富集区间信息;4)分析peak转录因子;5)分析与Peak关联基因的GO功能富集、KEGG通路富集情况;6)分析差异关联基因基本情况;7)分析差异关联基因的GO功能富集情况;8)分析差异关联基因的KEGG通路富集情况。结果1.提取冻存组织细胞核:在显微镜下观察到细胞核计数>100000,表示细胞核提取成功。2.测序文库构建后,用qubit软件检查测序文库,结果显示合格。3.生物信息分析结果:1)实验组与参考基因库之间的数据相似程度>98%(测序数据良好),可进行下一步检测;2)多房棘球蚴病组和健康小鼠组的reads在TSS明显起峰;3)通过单个样本的富集,筛选出显著性Peak;4)与peak关联的转录因子主要集中在zf-C2H2、Homeobox和BHLH等;5)与Peak关联基因的GO功能主要富集在细胞蛋白大分子定位、细胞发育调节、解剖结构形态调控等生物学过程,与peak关联基因的KEGG通路主要富集在MAPK、cGMP-PKG、Hippo等信号通路;6)多房棘球蚴病组与健康小鼠组的组蛋白H3K4ME1存在5547个差异关联基因,其中上调基因2556个、下调基因2929个;7)组蛋白H3K4ME1差异关联基因GO功能富集分析的生物过程主要有细胞投射组织的正向调节、GTPase的活性调节等,细胞组分主要有细胞投影膜、突触等,分子功能主要有肌动蛋白结合、细胞黏附分子结合等;8)组蛋白H3K4ME1差异关联基因KEGG通路富集分析主要分布在MAPK、Wnt、Rap1等信号通路上。结论获得了多房棘球蚴病组蛋白H3K4ME1的生物学功能和信号通路信息。 展开更多
关键词 多房棘球蚴病 组蛋白h3k4me1 生物学 信号通路
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The expression of Lin28B was co-regulated by H3K4me2 and Wnt5a/β-catenin/TCF7L2
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作者 ZHANG Ya-ni HU Cai +2 位作者 WANG Ying-jie ZUO Qi-sheng LI Bi-chun 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2020年第12期3054-3064,共11页
Lin28A and Lin28B are homologous RNA-binding proteins that participate in the development of primordial germ cells. The mechanisms underlying expression and regulation of Lin28A have been well documented, but such inf... Lin28A and Lin28B are homologous RNA-binding proteins that participate in the development of primordial germ cells. The mechanisms underlying expression and regulation of Lin28A have been well documented, but such information for Lin28B is limited. In this study, a fragment of the Lin28B promoter was cloned, the pEGFP-pLin28B vector was constructed. DF-1 chicken fibroblasts were transfected and the expression of green fluorescent protein (GFP) was measured. Furtherly, Lin28B promoter of different lengths fragments was cloned using the chromosome-walking method and the fragments were ligated into the PGL3-Basic vector, and transfected into DF-1 cells. Results of dual-luciferase reporter assay showed that the core of the Lin28B promoter was included in the sequence from –1 431 to –1 034 bp. The binding sites of the transcription factor TCF7L2 was showed within this sequence by bioinformatics analysis. The promoter activity of Lin28B was downregulated (P<0.05) when the TCF7L2 binding site was mutated. Further experiments suggested that Lin28B promoter activity responded to the activation or inhibition of Wnt signaling. Results of chromatin immunoprecipitation and quantitative PCR showed that β-catenin-TCF7L2 may be enriched in the Lin28B promoter core area. In vivo and in vitro activation or inhibition of Wnt signaling significantly up- or down-regulated (P<0.05) Lin28B expression. H3K4me2 enriched in the promoter of Lin28B, which affected the regulation of Wnt signaling to Lin28B. In conclusion, our results showed that H3K4me2 and Wnt5a/β-catenin/TCF7L2 were the positive regulators of Lin28B expression. Findings of this study may lay a theoretical foundation for illuminating the mechanism underlying Lin28B expression. 展开更多
关键词 primordial germ cells Lin28B PROMOTER h3k4me2 Wnt5a/β-catenin/TCF7L2
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镧暴露对子代大鼠学习记忆及海马组蛋白H3K4me3表达的影响
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作者 郭志新 王军 +3 位作者 王泓颖 肖瑶 张馨心 刘慧颖 《中国工业医学杂志》 CAS 2023年第5期401-404,共4页
目的探讨镧暴露对子代大鼠学习记忆能力及海马组蛋白H3赖氨酸4三甲基化(H3K4me3)水平的影响。方法将24只SPF级雌性Wistar孕鼠随机分为对照组,2.5、5.0和10.0 g/L氯化镧(LaCl_(3))染毒组,其子代大鼠断乳后通过自由饮水方式按原浓度继续... 目的探讨镧暴露对子代大鼠学习记忆能力及海马组蛋白H3赖氨酸4三甲基化(H3K4me3)水平的影响。方法将24只SPF级雌性Wistar孕鼠随机分为对照组,2.5、5.0和10.0 g/L氯化镧(LaCl_(3))染毒组,其子代大鼠断乳后通过自由饮水方式按原浓度继续镧暴露。而后在不同时间采用Morris水迷宫实验检测子代大鼠的学习记忆能力,ELISA法测定海马中组蛋白甲基转移酶(HMT)的活性,Western blot法检测海马中H3K4me3和脑源性神经营养因子(BDNF)的蛋白表达水平。结果与对照组比较,出生后第14、21、28、35和49天LaCl_(3)染毒组子代大鼠体质量明显下降(P<0.05)。LaCl_(3)染毒组子代大鼠寻找逃逸平台的潜伏期延长(P<0.05),穿越平台次数和目标象限停留时间均减少(P<0.05),提示子代大鼠空间学习记忆能力受损;与对照组相比,LaCl_(3)染毒组子代大鼠海马HMT活性降低(P<0.05),H3K4me3和BDNF蛋白表达水平均降低(P<0.05),并呈剂量-反应关系。结论镧暴露导致子代大鼠学习记忆能力损伤可能与海马组蛋白H3K4me3表达下降有关。 展开更多
关键词 氯化镧(LaCl_(3)) 组蛋白H3赖氨酸4三甲基化(h3k4me3) 组蛋白甲基转移酶(HMT) 学习记忆 子代大鼠
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组蛋白去甲基化酶LSD1去除亲代组蛋白H3K4me2促进复制偶联的核小体装配
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作者 杨笑菡 《延安大学学报(医学科学版)》 2023年第3期16-22,共7页
目的探索真核细胞内影响与调控复制偶联的核小体组装及解聚的表观遗传学机制。方法人骨肉瘤细胞系(U2OS)转染对照和组蛋白H3K4去甲基化酶(lysine-specific demethylase 1,LSD1)siRNA,双胸苷阻滞或胸苷-诺考达唑联合阻滞同步化细胞,释放... 目的探索真核细胞内影响与调控复制偶联的核小体组装及解聚的表观遗传学机制。方法人骨肉瘤细胞系(U2OS)转染对照和组蛋白H3K4去甲基化酶(lysine-specific demethylase 1,LSD1)siRNA,双胸苷阻滞或胸苷-诺考达唑联合阻滞同步化细胞,释放后在不同时间点进行流式细胞术分析,检测LSD1敲低对细胞周期的影响;免疫印迹试验检测LSD1 siRNA敲低效率;U2OS细胞同步化后进行免疫荧光共聚焦显微镜观察,检测LSD1、组蛋白H3K4二甲基化、一甲基化(H3K4me2/1)在细胞周期中的表达水平;U2OS细胞转染对照、LSD1 siRNA后进行微球菌核酸酶(micrococcal nuclease,MNase)消化后检测核小体装配效率;免疫共沉淀实验检测与LSD1存在相互作用的体内蛋白。结果组蛋白H3K4去甲基化酶LSD1能促进复制偶联的核小体装配。结论复制前期LSD1催化亲代组蛋白H3K4me2去甲基化,导致H3K4me2被清除至一定水平,有助于复制偶联的核小体装配。本研究不仅揭示了LSD1之前未被阐明的生物学功能,同时拓宽了对表观遗传生物学功能的认知。 展开更多
关键词 复制 核小体装配 组蛋白H3K4去甲基化酶 组蛋白甲基化
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Transgenerational analysis of H3K4me3 and H3K27me3 by ChIP-Seq links epigenetic inheritance to metabolism
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作者 Ke An Fengxia Du +18 位作者 Hao Meng Guochao Li Minjie Zhang Zongzhi Liu Zitong Zhao Zilong Zhang Di Yu Dong Wang Caiyun Yang Wencui Ma Lin Yuan Meiting Zhou Lili Duan Li Jin Hui Li Yan Zhang Jianzhong Su Jie Qiao Yingli Sun 《Journal of Genetics and Genomics》 SCIE CAS CSCD 2018年第3期169-172,共4页
Histone methylation is a kind of important epigenetic modification which occurs on the lysine residue or arginine residue of histone tails(Zhang and Reinberg,2001).It takes part in multiple biological processes,incl... Histone methylation is a kind of important epigenetic modification which occurs on the lysine residue or arginine residue of histone tails(Zhang and Reinberg,2001).It takes part in multiple biological processes,including gene expression,genomic stability,stem cell maturity,genetic imprinting,mitosis and development(Fischle et al.,2005). 展开更多
关键词 Transgenerational analysis of h3k4me3 and H3K27me3 by ChIP-Seq links epigenetic inheritance to metabolism
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Association of H3K4me3 and CBX7 Levels to the Down-Regulation of <i>GKN</i>1 Gene Expression in Gastric Cancer Cells
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作者 Chiara Stella Di Stadio Filomena Altieri +4 位作者 Antonella Federico Giuseppina Miselli Maurizio Grillo Emilia Rippa Paolo Arcari 《Journal of Biosciences and Medicines》 2019年第5期146-156,共11页
Gastrokine 1 (GKN1) is a highly secreted gastric mucosal protein in normal individuals but strongly down-regulated or totally absent in gastric cancer subjects. An epigenetic mechanism might be responsible for GKN1 ge... Gastrokine 1 (GKN1) is a highly secreted gastric mucosal protein in normal individuals but strongly down-regulated or totally absent in gastric cancer subjects. An epigenetic mechanism might be responsible for GKN1 gene silencing probably through the activity of a transcription factor in association with the enzymes SUV39H1 and HDACs on the GKN1 promoter. In fact, compared to non-tumor tissues, a high increase of H3K9me3 level was observed in the corresponding tumor ones. Because H3K4me3 seems to be a possible epigenetic mark for active euchromatin, we try to verify the H3K4me3 level on the GKN1 promoter in gastric cancer tumor specimens. In addition, we also attempt to highlight if CBX7 could be the possible regulatory transcription factor correlated to GKN1 gene promoter. Therefore, we evaluated if the CBX7 expression levels could be associated with GKN1 down-regulation in gastric cancer. To this purpose, 2 pairs of non-tumor and tumor surgical specimens from patients with gastric cancer were analyzed for H3K4me3 by chromatin immunoprecipitation (ChiP) assays, and 9 pairs were instead analyzed by Western blotting for GKN1, and CBX7 expression levels, respectively. The results suggested that the observed increase of H3K4me3 in tumor samples was not in agreement with its proposed function whereas the expression of CBX7 was not associated with the down-regulation of GKN1. In particular, the expression levels of CBX7 in tumor samples might suggest a survival role in gastric cancer. 展开更多
关键词 CBX7 Gastrokine 1 Gastric Cancer EPIGENETICS H3K4 Methylation
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ALFIN-like proteins link histone H3K4me3 to H2A ubiquitination and coordinate diverse chromatin modifications in Arabidopsis
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作者 Xiao-Min Su Dan-Yang Yuan +6 位作者 Na Liu Zhao-Chen Zhang Minqi Yang Lin Li She Chen Yue Zhou Xin-Jian He 《Molecular Plant》 2025年第1期130-150,共21页
Trimethylation of histone H3K4(H3K4me3)is widely distributed at numerous actively transcribed protein-coding genes throughout the genome.However,the interplay between H3K4me3 and other chromatin modifications in plant... Trimethylation of histone H3K4(H3K4me3)is widely distributed at numerous actively transcribed protein-coding genes throughout the genome.However,the interplay between H3K4me3 and other chromatin modifications in plants remains poorly understood.In this study,we show that the Arabidopsis thaliana ALFIN-LIKE(AL)proteins contain a C-terminal PHD finger capable of binding to H3K4me3 and a PHD-associated AL(PAL)domain that interacts with components of the Polycomb repressive complex 1,thereby facilitating H2A ubiquitination(H2Aub)at H3K4me3-enriched genes throughout the genome.Furthermore,we demonstrate that loss of function of SDG2,encoding a key histone H3K4 methyltransferase,leads to a reduction in H3K4me3 level,which subsequently causes a genome-wide decrease in H2Aub,revealing a strong association between H3K4me3 and H2Aub.Finally,we discover that the PAL domain of AL proteins interacts with various other chromatin-related proteins or complexes,including those involved in regulating H2A.Z deposition,H3K27me3 demethylation,histone deacetylation,and chromatin accessibility.Our genome-wide analysis suggests that the AL proteins play a crucial role in coordinating H3K4me3 with multiple other chromatin modifications across the genome. 展开更多
关键词 ALFIN-like proteins PRC1 HISTONE h3k4me3 H2Aub H2A.Z
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H3K27me3 and H3K4me3 Chromatin Environment at Super-Induced Dehydration Stress Memory Genes of Arabidopsis thaliana 被引量:7
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作者 Ning Liu Michael Fromm Zoya Avramova 《Molecular Plant》 SCIE CAS CSCD 2014年第3期502-513,共12页
Pre-exposure to a stress may alter the plant's cellular, biochemical, and/or transcriptional responses during future encounters as a "memory' from the previous stress. Genes increasing transcription in response to ... Pre-exposure to a stress may alter the plant's cellular, biochemical, and/or transcriptional responses during future encounters as a "memory' from the previous stress. Genes increasing transcription in response to a first dehydra- tion stress, but producing much higher transcript levels in a subsequent stress, represent the super-induced 'transcription memory' genes in Arabidopsis thaliana. The chromatin environment (histone H3 tri-methylations of Lys 4 and Lys 27, H3K4me3, and H3K27me3) studied at five dehydration stress memory genes revealed existence of distinct memory- response subclasses that responded differently to CLF deficiency and displayed different transcriptional activities dur- ing the watered recovery periods. Among the most important findings is the novel aspect of the H3K27me3 function observed at specific dehydration stress memory genes. In contrast to its well-known role as a chromatin repressive mechanism at developmentally regulated genes, H3K27me3 did not prevent transcription from the dehydration stress- responding genes. The high H3K27me3 levels present during transcriptionally inactive states did not interfere with the transition to active transcription and with H3K4me3 accumulation. H3K4me3 and H3K27me3 marks function indepen- dently and are not mutually exclusive at the dehydration stress-responding memory genes. 展开更多
关键词 dehydration stress-response genes transcription memory genes h3k4me3 and H3K27me3 at memorygenes CLF Arabidopsis thaliana.
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The PHD1 finger of KDM5B recognizes unmodified H3K4 during the demethylation of histone H3K4me2/3 by KDM5B 被引量:4
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作者 Yan Zhang Huirong Yang +8 位作者 Xue Guo Naiyan Rong Yujiao Song Youwei Xu Wenxian Lan Xu Zhang Maili Liu Yanhui Xu Chunyang Cao 《Protein & Cell》 SCIE CAS CSCD 2014年第11期837-850,共14页
KDM5B is a histone H3K4me2/3 demethylase. The PHD1 domain of KDM5B is critical for demethylation, but the mechanism underlying the action of this domain is unclear. In this paper, we observed that PHDIKDMSB interacts ... KDM5B is a histone H3K4me2/3 demethylase. The PHD1 domain of KDM5B is critical for demethylation, but the mechanism underlying the action of this domain is unclear. In this paper, we observed that PHDIKDMSB interacts with unmethylated H3K4me0. Our NMR structure of PHDIKDMSB in complex with H3K4me0 revealed that the binding mode is slightly different from that of other reported PHD fingers. The disruption of this interaction by double mutations on the residues in the interface (L325A/D328A) decreases the H3K4me2/3 demethylation activity of KDM5B in cells by approximately 50% and increases the transcriptional repression of tumor suppressor genes by approximately twofold. These findings imply that PHDIKDMSB may help maintain KDM5B at target genes to mediate the demethylation activities of KDM5B. 展开更多
关键词 KDM5B PHD1 h3k4me0 demethylase repression structure
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CXXC finger protein 1 (CFP1) bridges the reshaping of genomic H3K4me3 signature to the advancement of lung adenocarcinoma 被引量:1
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作者 Tao Fan Chu Xiao +5 位作者 Hengchang Liu Yu Liu Liyu Wang He Tian Chunxiang Li Jie He 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2023年第10期5010-5022,共13页
Histone H3 lysine 4 trimethylation(H3K4me3)is a canonical chromatin modification associated with active gene transcription,playing a pivotal role in regulating various cellular functions.Components of the H3K4me3 meth... Histone H3 lysine 4 trimethylation(H3K4me3)is a canonical chromatin modification associated with active gene transcription,playing a pivotal role in regulating various cellular functions.Components of the H3K4me3 methyltransferase complex,known as the proteins associated with SET1(COMPASS),have been implicated in exerting cancer-protective or cancer-inhibitory effects through inducive H3K4me3 modification.However,the role of the indispensable non-catalytic component of COMPASS CXXC-type zinc finger protein 1(CFP1)in malignant progression remains unclear. 展开更多
关键词 protective h3k4me3 BRIDGES
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The Association Between H3K4me3 and Antisense Transcription 被引量:1
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作者 Peng Cui Wanfei Liu +8 位作者 Yuhui Zhao Qiang Lin Feng Ding Chengqi Xin Jianing Geng Shuhui Song Fanglin Sun Songnian Hu Jun Yu 《Genomics, Proteomics & Bioinformatics》 CAS CSCD 2012年第2期74-81,共8页
Histone H3 lysine 4 trimethylation (H3K4me3) is well known to occur in the promoter region of genes for transcription activation. How- ever, when investigating the H3K4me3 profiles in the mouse cerebrum and testis, ... Histone H3 lysine 4 trimethylation (H3K4me3) is well known to occur in the promoter region of genes for transcription activation. How- ever, when investigating the H3K4me3 profiles in the mouse cerebrum and testis, we discovered that H3K4me3 also has a significant enrichment at the 3' end of actively transcribed (sense) genes, named as 3'-H3K4me3. 3'-H3K4me3 is associated with ~15% of pro- tein-coding genes in both tissues. In addition, we examined the transcriptional initiation signals including RNA polymerase II (RNAPII) binding sites and Y-CAGE-tag that marks transcriptional start sites. Interestingly, we found that 3'-H3K4me3 is associated with the ini- tiation of antisense transcription. Furthermore, 3'-H3K4me3 modification levels correlate positively with the antisense expression levels of the associated sense genes, implying that 3'-H3K4me3 is involved in the activation of antisense transcription. Taken together, our findings suggest that H3K4me3 may be involved in the regulation of antisense transcription that initiates from the 3' end of sense genes. In addition, a positive correlation was also observed between the expression of antisense and the associated sense genes with 3'-H3K4me3 modification. More importantly, we observed the 3'-H3K4me3 enrichment among genes in human, fruitfly and Arabidopsis, and found that the sequences of 3'-H3K4me3-marked regions are highly conserved and essentially indistinguishable from known promoters in ver- tebrate. Therefore, we speculate that these 3'-H3K4me3-marked regions may serve as potential promoters for antisense transcription and 3'-H3K4me3 appear to be a universal epigenetic feature in eukaryotes. Our results provide a novel insight into the epigenetic roles of H3K4me3 and the regulatory mechanism of antisense transcription. 展开更多
关键词 Antisense initiation and activation Antisense transcription h3k4me3
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