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基于多视图双聚类方法分析不同哺乳动物早期胚胎发育基因激活差异
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作者 龙春伸 李伟 +1 位作者 梁鹏飞 左永春 《内蒙古大学学报(自然科学版)》 CAS 北大核心 2019年第5期479-490,共12页
大量分子生物学研究证实,哺乳动物早期胚胎发育具有严格的分子调控机制.但是,不同种类之间早期胚胎发育可能存在的调节差异和分子机理并不清楚.利用比较转录组学方法识别不同物种之间的保守共表达基因簇,对于深入揭示胚胎发育和器官分... 大量分子生物学研究证实,哺乳动物早期胚胎发育具有严格的分子调控机制.但是,不同种类之间早期胚胎发育可能存在的调节差异和分子机理并不清楚.利用比较转录组学方法识别不同物种之间的保守共表达基因簇,对于深入揭示胚胎发育和器官分化十分关键.多视图双聚类方法(Multi-view bi-clustering,MVBC)可以解决胚胎样本中的基因表达信号弱和噪声数据较多的问题,较传统两步法可以更好地找到保守的共表达基因簇.我们使用多视图双聚类这一新方法,在人、鼠和牛胚胎中共鉴定出114个共表达基因模块,并对其中包含数目较多、可信度高的29个基因簇进行了KEGG通路富集分析.结果表明,这些基因簇在三个物种早期胚胎发育中共享的通路大多是核小体与RNA转运等起着基础作用的通路,表明在三个物种间合子特异性转录和翻译机制的建立都相对保守.另外,还发现了在物种内具有相似表达模式的8组基因簇、同一功能通路可在多个基因簇富集,以及信号通路在整个胚胎早期发育过程中呈时序性表达的特点.本研究揭示了三个物种间早期胚胎基因表达模式与通路功能的关系,丰富了物种间早期胚胎发育过程的差异化知识,对进一步研究哺乳动物早期胚胎发育机制有一定帮助. 展开更多
关键词 早期胚胎发育 多视图双聚类 表达基因簇 功能分析
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非典型致病性大肠杆菌菌株
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作者 束弋 杨萌 杜琳 《生物制品快讯》 2004年第6期17-17,共1页
关键词 非典型致病性大肠杆菌 菌株 基因簇表达 毒力因子
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TAR克隆技术及其在微生物次级代谢产物研究中的应用 被引量:2
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作者 童瑞年 吴旭日 陈依军 《中国药科大学学报》 CAS CSCD 北大核心 2018年第2期129-135,共7页
微生物次级代谢产物结构多样、种类丰富,是新药发现的重要来源。微生物次级代谢产物由特定生物合成基因簇编码合成,通常与微生物的生长繁殖无关。由于实验室可培养微生物的数量较少,而且多数可培养微生物存在基因簇沉默的现象,严重阻碍... 微生物次级代谢产物结构多样、种类丰富,是新药发现的重要来源。微生物次级代谢产物由特定生物合成基因簇编码合成,通常与微生物的生长繁殖无关。由于实验室可培养微生物的数量较少,而且多数可培养微生物存在基因簇沉默的现象,严重阻碍了微生物来源药物的研究和开发。微生物生物合成基因簇的异源表达及生物合成相应的次级代谢产物已逐渐成为发现新颖活性化合物的有效手段之一。作为研究微生物次级代谢产物的重要工具,基于TAR(transformation associated recombination)克隆技术的异源表达策略可实现绝大多数基因簇的完整异源表达。本文从TAR克隆技术的原理、应用和策略改进3个方面,总结了基于TAR克隆技术的微生物次级代谢产物异源生物合成的研究进展,为研究和开发新型微生物来源药物提供方法学借鉴。 展开更多
关键词 TAR克隆技术 生物合成基因簇 次级代谢产物 基因簇异源表达 微生物药物
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基因簇大片段克隆技术研究进展及挑战 被引量:2
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作者 高花花 胡娟 刘玲丽 《微生物学通报》 CAS CSCD 北大核心 2023年第1期351-367,共17页
天然产物结构复杂、活性多样,是新药开发的重要来源,对天然产物生物合成途径的研究,有利于探索酶催化的合成机制,促进复杂天然产物的应用。天然产物的生物合成由其对应的基因簇调控,其中大量天然产物生物合成基因簇(biosynthetic gene c... 天然产物结构复杂、活性多样,是新药开发的重要来源,对天然产物生物合成途径的研究,有利于探索酶催化的合成机制,促进复杂天然产物的应用。天然产物的生物合成由其对应的基因簇调控,其中大量天然产物生物合成基因簇(biosynthetic gene clusters,BGCs)在野生型菌株中无法表达或表达量低。对这些基因簇的研究,需要进行克隆表达,而如何克隆大片段基因簇并使其表达,从而发现新型天然产物是一个具有挑战性的问题。其中构建基因组文库、转化关联重组(transformation-associated recombination,TAR)、Red/ET重组等是克隆大片段基因簇的重要技术。本文从克隆技术的策略和应用两个方面,总结了这3种克隆技术目前的研究进展,讨论了目前大片段基因簇克隆技术面临的挑战,为研究大片段基因簇提供方法学借鉴。 展开更多
关键词 天然产物 生物合成基因簇 基因组文库 转化关联重组 Red/ET 基因簇异源表达
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Floating Escherichia coli by Expressing Cyanobacterial Gas Vesicle Genes 被引量:1
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作者 WANG Tianhe KANG Li +15 位作者 LI Jiaheng WU Wenjie ZHANG Peiran GONG Minghao LAI Weihong ZHANG Chunyan CHANG Lei PENG Yong YANG Zhongzhou LI Lian BAO Yingying XU Haowen ZHANG Xiaohua SUI Zhenghong YANG Guanpin WANG Xianghong 《Journal of Ocean University of China》 SCIE CAS 2015年第1期84-88,共5页
Gas vesicles are hollow, air-filled polyprotein structures that provide the buoyancy to cells. They are found in a variety of prokaryotes. In this study, we isolated a partial gas vesicle protein gene cluster containi... Gas vesicles are hollow, air-filled polyprotein structures that provide the buoyancy to cells. They are found in a variety of prokaryotes. In this study, we isolated a partial gas vesicle protein gene cluster containing gvpA and gvpC20ψ from Planktothrix rubescens, and inserted it into an expression vector and expressed it in E. coli. The gas vesicle was developed in bacterial cells, which made bacterial cells to float on medium surface. We also amplified gvpA and gvpC20ψ separately and synthesized an artificial operon by fusing these two genes with the standardized gene expression controlling elements of E. coli. The artificial operon was expressed in E. coli, forming gas vesicles and floating bacteria cells. Our findings verified that the whole set of genes and the overall structure of gas vesicle gene cluster are not necessary for developing gas vesicles in bacteria cells. Two genes, gvpA and gvpC20ψ, of the gas vesicle gene cluster are sufficient for synthesizing an artificial operon that can develop gas vesicles in bacteria cells. Our findings provided a wide range of applications including easing the harvest of cultured microalgae and bacteria, as well as enriching and remediating aquatic pollutants by constructing gas vesicles in their ceils. 展开更多
关键词 gas vesicle gene cluster gas vesicle gene BUOYANCY
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Exploring CTCF and cohesin related chromatin architecture at HOXA gene cluster in primary human fibroblasts 被引量:2
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作者 WANG Xing XU Miao +4 位作者 ZHAO GuangNian LIU GuoYou HAO DeLong LV Xiang LIU DePei 《Science China(Life Sciences)》 SCIE CAS CSCD 2015年第9期860-866,共7页
Spatial expression patterns of homeobox (HOX) genes delineate positional identity of primary fibroblasts from different topo- graphic sites. The molecular mechanism underlying the establishing or maintaining of HOX ... Spatial expression patterns of homeobox (HOX) genes delineate positional identity of primary fibroblasts from different topo- graphic sites. The molecular mechanism underlying the establishing or maintaining of HOX gene expression pattern remains an attractive developmental issue to be addressed. Our previous work suggested a critical role of CTCF/cobesin-mediated high- er-order chromatin structure in RA-induced HOXA activation in human teratocarcinoma NT2/D1 cells. This study investigated the recruitment of CTCF and cohesin, and the higher-order chromatin structure of the HOXA locus in fetal lung and adult foreskin fibroblasts, which display complementary HOXA gene expression patterns. Chromatin contacts between the CTCF-binding sites were observed with lower frequency in human foreskin fibroblasts. This observation is consistent with the lower level of cohesin recruitment and 5' HOXA gene expression in the same cells. We also showed that CTCF-binding site A56 (CBSA56) related chromatin structures exhibit the most notable changes in between the two types of cell, and hence may stand for one of the key CTCF-binding sites for cell-type specific chromatin structure organization. Together, these results im- ply that CTCF/cohesin coordinates HOXA cluster higher-order chromatin structure and expression during development, and provide insight into the relationship between cell-type specific chromatin organization and the spatial collinearity. 展开更多
关键词 human fibroblasts HOXA cluster higher-order chromatin structure CTCF COHESION
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Mining of a streptothricin gene cluster from Streptomyces sp.TP-A0356 genome via heterologous expression 被引量:4
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作者 LI JinE GUO ZhengYan +4 位作者 HUANG Wei MENG XiangXi AI GuoMin TANG GongLi CHEN YiHua 《Science China(Life Sciences)》 SCIE CAS 2013年第7期619-627,1-4,共9页
Streptothricins (STs) are used commercially to treat bacterial and fungal diseases in agriculture. Mining of the sequenced microbial genomes uncovered two cryptic ST clusters from Streptomyces sp. C and Streptomyces s... Streptothricins (STs) are used commercially to treat bacterial and fungal diseases in agriculture. Mining of the sequenced microbial genomes uncovered two cryptic ST clusters from Streptomyces sp. C and Streptomyces sp. TP-A0356. The ST cluster from S. sp. TP-A0356 was verified by successful heterologous expression in Streptomyces coelicolor M145. Two new ST analogs were produced together with streptothricin F and streptothricin D in the heterologous host. The ST cluster was further confirmed by inactivation of gene stnO, which was proposed encoding an aminomutase supplying -lysines for the poly-β-Lys chain formation. A putative biosynthetic pathway for STs is proposed based on bioinformatics analyses of the ST genes and experimental evidence. 展开更多
关键词 genome mining streptothricin STREPTOMYCES heterologous expression BIOSYNTHESIS
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