Objective Hepatocyte nuclear factor 4-alpha(HNF4A)is a critical transcription factor in the liver and pancreas.Dysfunctions of HNF4A lead to maturity onset diabetes of the young 1(MODY1).Notably,MODY1 patients with HN...Objective Hepatocyte nuclear factor 4-alpha(HNF4A)is a critical transcription factor in the liver and pancreas.Dysfunctions of HNF4A lead to maturity onset diabetes of the young 1(MODY1).Notably,MODY1 patients with HNF4A pathogenic mutations exhibit decreased responses to arginine and reduced plasma triglyceride levels,but the mechanisms remain unclear.This study aims to investigate the potential target genes transcriptionally regulated by HNF4A and explore its role in these metabolic pathways.Methods A stable 293T cell line expressing the HNF1A reporter was overexpressed with HNF4A.RNA sequencing(RNA-seq)was performed to analyze transcriptional differences.Transcription factor binding site prediction was then conducted to identify HNF4A binding motifs in the promoter regions of relevant target genes.Results RNA-seq results revealed a significant upregulation of transmembrane 4 L six family member 5(TM4SF5)mRNA in HNF4A-overexpressing cells.Transcription factor binding predictions suggested the presence of five potential HNF4A binding motifs in the TM4SF5 promoter.Finally,we confirmed that the DR1 site in the-57 to-48 region of the TM4SF5 promoter is the key binding motif for HNF4A.Conclusion This study identified TM4SF5 as a target gene of HNF4A and determined the key binding motif involved in its regulation.Given the role of TM4SF5 as an arginine sensor in mTOR signaling activation and triglyceride secretion,which closely aligns with phenotypes observed in MODY1 patients,our findings provide novel insights into the possible mechanisms by which HNF4A regulates triglyceride secretion in the liver and arginine-stimulated insulin secretion in the pancreas.展开更多
社区搜索的目标是从数据图中得到包含查询顶点的紧密子图,在社会学、生物学等领域有着广泛应用。针对现有基于子图连通性的社区模型的基础连通结构都是完全连通图,无法满足实际应用中用户对社区结构多样性的需求的问题,提出一种基于moti...社区搜索的目标是从数据图中得到包含查询顶点的紧密子图,在社会学、生物学等领域有着广泛应用。针对现有基于子图连通性的社区模型的基础连通结构都是完全连通图,无法满足实际应用中用户对社区结构多样性的需求的问题,提出一种基于motif连通性的社区搜索方法,其中包括基于motif连通性的社区(MCC)模型以及两个相应的社区搜索算法——MPCS(Motif-Processed Community Search)算法和基于MP-index的社区搜索算法。MCC模型可以协助用户自由指定社区的基础连通结构,MPCS算法可以用来解决MCC的搜索问题。此外,提出两个分别针对motif实例搜索过程及所属社区判断过程的剪枝优化技术。最后,设计了MP-index以避免社区搜索过程中的冗余遍历操作。在多个真实数据集上进行实验的结果表明:剪枝优化可以使MPCS算法的耗时减少60%~85%,而基于MP-index的社区搜索算法相较于加入剪枝优化的MPCS算法,效率提升普遍达到了2~3个数量级。可见,所提方法在商品推荐和社交网络等问题上有着实际应用价值。展开更多
利用核酸i-motif结构对质子的超敏感特性,选择富含胞嘧啶C的核酸链及其互补链,以及染料SYBR Green Ⅰ对单双链DNA的不同荧光响应特性,研制了一种灵敏的新型pH响应荧光传感器。当pH值从5.0变为7.5时,SYBR Green Ⅰ的荧光强度增大了4倍以...利用核酸i-motif结构对质子的超敏感特性,选择富含胞嘧啶C的核酸链及其互补链,以及染料SYBR Green Ⅰ对单双链DNA的不同荧光响应特性,研制了一种灵敏的新型pH响应荧光传感器。当pH值从5.0变为7.5时,SYBR Green Ⅰ的荧光强度增大了4倍以上,pH传感范围是5.0～7.5,并显示出很高的pH分辨率(0.1个pH单元)。该pH传感器具有简单、快速、成本低等优点,有望用于相关生物过程中微小pH值变化的传感分析。展开更多
i-Motif is formed from two parallel duplexes by intercalating with each other in an antiparallel orientation and each duplex is held together-via-hemiprotonated cytosine+-cytosine base pairs.However,a cell is crowded ...i-Motif is formed from two parallel duplexes by intercalating with each other in an antiparallel orientation and each duplex is held together-via-hemiprotonated cytosine+-cytosine base pairs.However,a cell is crowded with various biomolecules and little is known about the properties of i-Motif under molecular crowding conditions until now.In the present study,we used human telomeric DNA sequence,[C3TA23C3,as a model system to investigate such problem by circular dichroism(CD) and UV absorbance spectroscopy.Based on the CD spectra,we found that there were no changes about the structure of i-Motif in the presence of polyethylene glycol(PEG).CD melting results showed that the thermal stability of i-Motif was increased under molecular crowding conditions compare to that in dilute buffer,which was further demonstrated by UV-melting results.This work suggests that molecular crowding could not affect the structure of i-Motif,which may depend on pH,while could enhance the thermal stability of i-Motif.展开更多
文摘Objective Hepatocyte nuclear factor 4-alpha(HNF4A)is a critical transcription factor in the liver and pancreas.Dysfunctions of HNF4A lead to maturity onset diabetes of the young 1(MODY1).Notably,MODY1 patients with HNF4A pathogenic mutations exhibit decreased responses to arginine and reduced plasma triglyceride levels,but the mechanisms remain unclear.This study aims to investigate the potential target genes transcriptionally regulated by HNF4A and explore its role in these metabolic pathways.Methods A stable 293T cell line expressing the HNF1A reporter was overexpressed with HNF4A.RNA sequencing(RNA-seq)was performed to analyze transcriptional differences.Transcription factor binding site prediction was then conducted to identify HNF4A binding motifs in the promoter regions of relevant target genes.Results RNA-seq results revealed a significant upregulation of transmembrane 4 L six family member 5(TM4SF5)mRNA in HNF4A-overexpressing cells.Transcription factor binding predictions suggested the presence of five potential HNF4A binding motifs in the TM4SF5 promoter.Finally,we confirmed that the DR1 site in the-57 to-48 region of the TM4SF5 promoter is the key binding motif for HNF4A.Conclusion This study identified TM4SF5 as a target gene of HNF4A and determined the key binding motif involved in its regulation.Given the role of TM4SF5 as an arginine sensor in mTOR signaling activation and triglyceride secretion,which closely aligns with phenotypes observed in MODY1 patients,our findings provide novel insights into the possible mechanisms by which HNF4A regulates triglyceride secretion in the liver and arginine-stimulated insulin secretion in the pancreas.
文摘社区搜索的目标是从数据图中得到包含查询顶点的紧密子图,在社会学、生物学等领域有着广泛应用。针对现有基于子图连通性的社区模型的基础连通结构都是完全连通图,无法满足实际应用中用户对社区结构多样性的需求的问题,提出一种基于motif连通性的社区搜索方法,其中包括基于motif连通性的社区(MCC)模型以及两个相应的社区搜索算法——MPCS(Motif-Processed Community Search)算法和基于MP-index的社区搜索算法。MCC模型可以协助用户自由指定社区的基础连通结构,MPCS算法可以用来解决MCC的搜索问题。此外,提出两个分别针对motif实例搜索过程及所属社区判断过程的剪枝优化技术。最后,设计了MP-index以避免社区搜索过程中的冗余遍历操作。在多个真实数据集上进行实验的结果表明:剪枝优化可以使MPCS算法的耗时减少60%~85%,而基于MP-index的社区搜索算法相较于加入剪枝优化的MPCS算法,效率提升普遍达到了2~3个数量级。可见,所提方法在商品推荐和社交网络等问题上有着实际应用价值。
文摘利用核酸i-motif结构对质子的超敏感特性,选择富含胞嘧啶C的核酸链及其互补链,以及染料SYBR Green Ⅰ对单双链DNA的不同荧光响应特性,研制了一种灵敏的新型pH响应荧光传感器。当pH值从5.0变为7.5时,SYBR Green Ⅰ的荧光强度增大了4倍以上,pH传感范围是5.0～7.5,并显示出很高的pH分辨率(0.1个pH单元)。该pH传感器具有简单、快速、成本低等优点,有望用于相关生物过程中微小pH值变化的传感分析。
文摘i-Motif is formed from two parallel duplexes by intercalating with each other in an antiparallel orientation and each duplex is held together-via-hemiprotonated cytosine+-cytosine base pairs.However,a cell is crowded with various biomolecules and little is known about the properties of i-Motif under molecular crowding conditions until now.In the present study,we used human telomeric DNA sequence,[C3TA23C3,as a model system to investigate such problem by circular dichroism(CD) and UV absorbance spectroscopy.Based on the CD spectra,we found that there were no changes about the structure of i-Motif in the presence of polyethylene glycol(PEG).CD melting results showed that the thermal stability of i-Motif was increased under molecular crowding conditions compare to that in dilute buffer,which was further demonstrated by UV-melting results.This work suggests that molecular crowding could not affect the structure of i-Motif,which may depend on pH,while could enhance the thermal stability of i-Motif.
