人类β-地中海贫血的发病机制与β-样珠蛋白基因异常表达息息相关。人类β-样珠蛋白基因以5′-ε-Gγ-Aγ-δ-β-3′的顺序排列于β-珠蛋白基因座,受5′LCR (locus control region)中5个超敏位点(hypersensitive site,HS)5′HS5~5′HS1...人类β-地中海贫血的发病机制与β-样珠蛋白基因异常表达息息相关。人类β-样珠蛋白基因以5′-ε-Gγ-Aγ-δ-β-3′的顺序排列于β-珠蛋白基因座,受5′LCR (locus control region)中5个超敏位点(hypersensitive site,HS)5′HS5~5′HS1和3′HS1调控。其中5′HS2是最重要的增强子,能产生增强子RNA(enhancerRNA)并调控ε-globin、γ-globin和β-globin的表达。为了进一步探究K562细胞中增强子5′HS2的功能,本研究首先通过染色质构象捕获技术在人慢性髓原白血病K562细胞中探测到5′HS2介导的染色质相互作用集中在以包含CTCF(CCCTC-bindingfactor)位点的3′HS1和5′HS5为边界的拓扑结构域中,5′HS2在三维空间上与HBE1、HBG2和HBG1启动子区域相互靠近。其次运用CRISPRDNA片段编辑技术在K562细胞系中删除了增强子5′HS2。最后通过RNA-seq和CUT&Tag (cleavage under target&tagmentation)实验分析两个5′HS2删除的单克隆细胞系的转录组和染色质H3K27ac组蛋白修饰,发现91个基因表达显著下调而且其启动子区的H3K27ac修饰程度显著降低。这些基因主要聚类于氧气运输、免疫应答、细胞粘附、抗氧化和维持血栓形成等与红细胞功能相关的生物过程中,表明K562细胞系中增强子5′HS2对红细胞功能相关基因的转录产生了广泛影响。展开更多
Based on monolayer dispersion theory,Co_(3)O_(4)/ZSM-5 catalysts with different loadings have been prepared for selective catalytic reduction of nitrogen oxides by ammonia.Co_(3)O_(4)can spontaneously disperse on HZSM...Based on monolayer dispersion theory,Co_(3)O_(4)/ZSM-5 catalysts with different loadings have been prepared for selective catalytic reduction of nitrogen oxides by ammonia.Co_(3)O_(4)can spontaneously disperse on HZSM-5 support with a monolayer dispersion threshold of 0.061 mmol 100 m^(-2),equaling to a weight percentage around 4.5%.It has been revealed that the quantities of surface active oxygen(O_(2)^(-))and acid sites are crucial for the reaction,which can adsorb and activate NO_(x)and NH_(3)reactants effectively.Below the monolayer dispersion threshold,Co_(3)O_(4)is finely dispersed as sub-monolayers or monolayers and in an amorphous state,which is favorable to generate the two kinds of active sites,hence promoting the performance of ammonia selective catalytic reduction of nitrogen oxide.However,the formation of crystalline Co_(3)O_(4)above the capacity is harmful to the reaction performance.4%Co_(3)O_(4)/ZSM-5,the catalyst close to the monolayer dispersion capacity,possesses the most abundant active O_(2)^(-)species and acidic sites,thereby demonstrating the best reaction performance in all the samples.It is proposed the optimal Co_(3)O_(4)/ZSM-5 catalyst can be prepared by loading the capacity amount of Co_(3)O_(4)onto HZSM-5 support.展开更多
文摘人类β-地中海贫血的发病机制与β-样珠蛋白基因异常表达息息相关。人类β-样珠蛋白基因以5′-ε-Gγ-Aγ-δ-β-3′的顺序排列于β-珠蛋白基因座,受5′LCR (locus control region)中5个超敏位点(hypersensitive site,HS)5′HS5~5′HS1和3′HS1调控。其中5′HS2是最重要的增强子,能产生增强子RNA(enhancerRNA)并调控ε-globin、γ-globin和β-globin的表达。为了进一步探究K562细胞中增强子5′HS2的功能,本研究首先通过染色质构象捕获技术在人慢性髓原白血病K562细胞中探测到5′HS2介导的染色质相互作用集中在以包含CTCF(CCCTC-bindingfactor)位点的3′HS1和5′HS5为边界的拓扑结构域中,5′HS2在三维空间上与HBE1、HBG2和HBG1启动子区域相互靠近。其次运用CRISPRDNA片段编辑技术在K562细胞系中删除了增强子5′HS2。最后通过RNA-seq和CUT&Tag (cleavage under target&tagmentation)实验分析两个5′HS2删除的单克隆细胞系的转录组和染色质H3K27ac组蛋白修饰,发现91个基因表达显著下调而且其启动子区的H3K27ac修饰程度显著降低。这些基因主要聚类于氧气运输、免疫应答、细胞粘附、抗氧化和维持血栓形成等与红细胞功能相关的生物过程中,表明K562细胞系中增强子5′HS2对红细胞功能相关基因的转录产生了广泛影响。
基金the financial supporting by the National Natural Science Foundation of China(Grant Nos.21962009,22172071,22102069,22062013)the Natural Science Foundation of Jiangxi Province(Grant Nos.20202BAB203006,20181ACB20005)the Key Laboratory Foundation of Jiangxi Province for Environment and Energy Catalysis(Grant No.20181BCD40004).
文摘Based on monolayer dispersion theory,Co_(3)O_(4)/ZSM-5 catalysts with different loadings have been prepared for selective catalytic reduction of nitrogen oxides by ammonia.Co_(3)O_(4)can spontaneously disperse on HZSM-5 support with a monolayer dispersion threshold of 0.061 mmol 100 m^(-2),equaling to a weight percentage around 4.5%.It has been revealed that the quantities of surface active oxygen(O_(2)^(-))and acid sites are crucial for the reaction,which can adsorb and activate NO_(x)and NH_(3)reactants effectively.Below the monolayer dispersion threshold,Co_(3)O_(4)is finely dispersed as sub-monolayers or monolayers and in an amorphous state,which is favorable to generate the two kinds of active sites,hence promoting the performance of ammonia selective catalytic reduction of nitrogen oxide.However,the formation of crystalline Co_(3)O_(4)above the capacity is harmful to the reaction performance.4%Co_(3)O_(4)/ZSM-5,the catalyst close to the monolayer dispersion capacity,possesses the most abundant active O_(2)^(-)species and acidic sites,thereby demonstrating the best reaction performance in all the samples.It is proposed the optimal Co_(3)O_(4)/ZSM-5 catalyst can be prepared by loading the capacity amount of Co_(3)O_(4)onto HZSM-5 support.
