The myeloperoxidase (MPO) is an important microbicidal protein present at high concentration in the primary granule of mature granulocyte and its expression is regulated in both myeloidcell-lineage and premyelocytic-s...The myeloperoxidase (MPO) is an important microbicidal protein present at high concentration in the primary granule of mature granulocyte and its expression is regulated in both myeloidcell-lineage and premyelocytic-stagespecific manners. A better understanding of the underlying control mechanisms should provide insights into the temporal and co-ordinate regulation of the gene expression during granulopoiesis. We have identified its promoter by mapping the start(s) of transcription using various molecular approaches together with demonstrating the promoter function of the relevant DNA segment in a transient transfection reporter assay. Besides the major start of transcription mapped at G residue, 11 nucleotide upstream of the 3’ end of exon 0, the usage of that is specific to the MPO expressing cell lines, we have shown that irrespective of the MPO-expression status of the hematopoietic cells, transcription occurs broadly within a two kb region upstream of the 5’ proximity of the gene, and is largely terminated in nitron 2. These data support a model of the pre myelocytic-stage-specific MPO expression, the control of which is operated at initiation as well as elongation levels of transcription.展开更多
GABAergic neurons are the major inhibitory interneurons that powerfully control the function of spinal neuronal networks.In recent years,tremendous progresses have been made in understanding the transcriptional contro...GABAergic neurons are the major inhibitory interneurons that powerfully control the function of spinal neuronal networks.In recent years,tremendous progresses have been made in understanding the transcriptional control of GABAergic neuron development in the dorsal spinal cord.New experimental approaches provide a relatively high throughput way to study the molecular regulation of subgroup fate determination.Our understanding of the molecular mechanisms on GABAergic neuron development in the dorsal spinal cord is rapidly expanding.Recent studies have defined several transcription factors that play essential roles in GABAergic neuron development in the spinal dorsal horn.Here,we review results of very recent analyses of the mechanisms that specify the GABAergic neuron development in the dorsal spinal cord,especially the progresses in the homeodomain(HD) and basic-helix-loop-helix(bHLH) containing transcription factors.展开更多
瓜楼素（trichosathin）是一种核糖体钝化蛋白,是从一种中药植物瓜楼的根中发现的。纯化的α-瓜楼素可引起人免疫缺陷性病毒（HIV）在严重感染的 CD<sub>4</sub><sup>+</sup>细胞中复制的浓度依赖性抑制。为了...瓜楼素（trichosathin）是一种核糖体钝化蛋白,是从一种中药植物瓜楼的根中发现的。纯化的α-瓜楼素可引起人免疫缺陷性病毒（HIV）在严重感染的 CD<sub>4</sub><sup>+</sup>细胞中复制的浓度依赖性抑制。为了进一步研究钝化及其突变文本对 HIV 作用的精确机理,需大量蛋白和用于再生和分析突变体的系统。由此,Bioso-展开更多
Objective To explore the role and regulation of guanine nucleotide-binding protein G（i）, a-1 subunit （GNAI1） in hepatocellular carcinoma （HCC）. Methods Expression of GNAI1 in HCC samples was determined by qRT-PC...Objective To explore the role and regulation of guanine nucleotide-binding protein G（i）, a-1 subunit （GNAI1） in hepatocellular carcinoma （HCC）. Methods Expression of GNAI1 in HCC samples was determined by qRT-PCR and immunohistochemical （IHC） staining. Huh-7 and SNU-387 cells stably expressing GNAI1 were established by the infection of lentivirus transducing unit containing GNAI1. siRNA against GNAI1 was transfected into SMMC-7721 cells to knock down the GNAI1 expression in HCC cells. Mir-320a/c/d mimics were transfected into SMMC-7721 and SK-Hep-1 cells and the expression of GNAll was determined by Western blot. The migration and invasion of Huh-7, SNU-387, SK-Hep-1 and SMMC-7721 cells were investigated by Transwell assays. Results The GNAI1 protein was significantly downregulated in HCC samples without changes in its mRNA levels. GNAI1 could inhibit the migration and invasion of HCC cells in vitro. Further investigations indicated that GNAI1 was a target of miR-320a/c/d in HCC cells. Transwell assays demonstrated that these microRNAs could promote the migratory ability and invasivesess of HCC cells in vitro. Conclusions GNAII is downregulated in HCC and inhibits the migration and invasion of HCC cells. This study is the first to investigate the role of GNAI1 in cancer. Regulation of GNAI1 by miR-320a/c/d indicates new therapeutic avenues for targeting HCC metastasis.展开更多
Chromatin immtmoprecipitation followed by sequencing （ChlP-sec0 is increasingly being used for genome-wide profiling of transcriptional regulation, as this technique enables dissection of the gene regulatory networks...Chromatin immtmoprecipitation followed by sequencing （ChlP-sec0 is increasingly being used for genome-wide profiling of transcriptional regulation, as this technique enables dissection of the gene regulatory networks. With input as control, a variety of statistical methods have been proposed for identifying the enriched regions in the genome, i.e., the transcriptional factor binding sites and chromatin modifications. However, when there are no controls, whether peak calling is still reliable awaits systematic evaluations. To address this question, we used a Bayesian framework approach to show the effectiveness of peak calling without controls （PCWC）. Using several different types of ChlP-seq data, we demonstrated the relatively high accuracy of PCWC with less than a 5% false discovery rate （FDR）. Compared with previously published methods, e.g., the model-based analysis of ChlP-seq （MACS）, PCWC is reliable with lower FDR. Furthermore, to interpret the biological significance of the called peaks, in combination with microarray gene expression data, gene ontology annotation and subsequent motif discovery, our results indicate PCWC possesses a high efficiency. Additionally, using in silico data, only a small number of peaks were identified, suggesting the significantly low FDR for PCWC.展开更多
Skeletal muscle fitness plays vital roles in human health and disease and is determined by developmental as well as physiological inputs. These inputs control and coordinate muscle fiber programs, including capacity f...Skeletal muscle fitness plays vital roles in human health and disease and is determined by developmental as well as physiological inputs. These inputs control and coordinate muscle fiber programs, including capacity for fuel burning, mitochondrial ATP production, and contraction. Recent studies have demonstrated crucial roles for nuclear receptors and their co-activators, and micro RNAs(mi RNAs) in the regulation of skeletal muscle energy metabolism and fiber type determination. In this review, we present recent progress in the study of nuclear receptor signaling and mi RNA networks in muscle fiber type switching. We also discuss the therapeutic potential of nuclear receptors and mi RNAs in disease states that are associated with loss of muscle fitness.展开更多
文摘The myeloperoxidase (MPO) is an important microbicidal protein present at high concentration in the primary granule of mature granulocyte and its expression is regulated in both myeloidcell-lineage and premyelocytic-stagespecific manners. A better understanding of the underlying control mechanisms should provide insights into the temporal and co-ordinate regulation of the gene expression during granulopoiesis. We have identified its promoter by mapping the start(s) of transcription using various molecular approaches together with demonstrating the promoter function of the relevant DNA segment in a transient transfection reporter assay. Besides the major start of transcription mapped at G residue, 11 nucleotide upstream of the 3’ end of exon 0, the usage of that is specific to the MPO expressing cell lines, we have shown that irrespective of the MPO-expression status of the hematopoietic cells, transcription occurs broadly within a two kb region upstream of the 5’ proximity of the gene, and is largely terminated in nitron 2. These data support a model of the pre myelocytic-stage-specific MPO expression, the control of which is operated at initiation as well as elongation levels of transcription.
基金the National Natural Science Foundation of China (30470556)the Program for New Century Excellent Talents in University
文摘GABAergic neurons are the major inhibitory interneurons that powerfully control the function of spinal neuronal networks.In recent years,tremendous progresses have been made in understanding the transcriptional control of GABAergic neuron development in the dorsal spinal cord.New experimental approaches provide a relatively high throughput way to study the molecular regulation of subgroup fate determination.Our understanding of the molecular mechanisms on GABAergic neuron development in the dorsal spinal cord is rapidly expanding.Recent studies have defined several transcription factors that play essential roles in GABAergic neuron development in the spinal dorsal horn.Here,we review results of very recent analyses of the mechanisms that specify the GABAergic neuron development in the dorsal spinal cord,especially the progresses in the homeodomain(HD) and basic-helix-loop-helix(bHLH) containing transcription factors.
文摘瓜楼素（trichosathin）是一种核糖体钝化蛋白,是从一种中药植物瓜楼的根中发现的。纯化的α-瓜楼素可引起人免疫缺陷性病毒（HIV）在严重感染的 CD<sub>4</sub><sup>+</sup>细胞中复制的浓度依赖性抑制。为了进一步研究钝化及其突变文本对 HIV 作用的精确机理,需大量蛋白和用于再生和分析突变体的系统。由此,Bioso-
基金supported by grants from the National 973 Key Basic Research Program(No.2011CB933100)National Natural Science Foundation of China(No.81125016 and 81101481)+1 种基金Science and Technology Commission of Shanghai Municipality(No.11XD1404500 and 10JC1414200)Shanghai Health Bureau(No.XYQ2011047 and XBR2011039)
文摘Objective To explore the role and regulation of guanine nucleotide-binding protein G（i）, a-1 subunit （GNAI1） in hepatocellular carcinoma （HCC）. Methods Expression of GNAI1 in HCC samples was determined by qRT-PCR and immunohistochemical （IHC） staining. Huh-7 and SNU-387 cells stably expressing GNAI1 were established by the infection of lentivirus transducing unit containing GNAI1. siRNA against GNAI1 was transfected into SMMC-7721 cells to knock down the GNAI1 expression in HCC cells. Mir-320a/c/d mimics were transfected into SMMC-7721 and SK-Hep-1 cells and the expression of GNAll was determined by Western blot. The migration and invasion of Huh-7, SNU-387, SK-Hep-1 and SMMC-7721 cells were investigated by Transwell assays. Results The GNAI1 protein was significantly downregulated in HCC samples without changes in its mRNA levels. GNAI1 could inhibit the migration and invasion of HCC cells in vitro. Further investigations indicated that GNAI1 was a target of miR-320a/c/d in HCC cells. Transwell assays demonstrated that these microRNAs could promote the migratory ability and invasivesess of HCC cells in vitro. Conclusions GNAII is downregulated in HCC and inhibits the migration and invasion of HCC cells. This study is the first to investigate the role of GNAI1 in cancer. Regulation of GNAI1 by miR-320a/c/d indicates new therapeutic avenues for targeting HCC metastasis.
基金Foundation items： This study was supported by the National 973 project of China （2011CBA01101） and the National Natural Science Foundation of China （30871343 and 31130051 ） Acknowledgments： We are thankful to Shao-Bin XU （Kunming Institute of Zoology, CAS） for his support on super-computing service, and to Yu-qi ZHAO （Kunming Institute of Zoology, CAS） for his helpful discussion.
文摘Chromatin immtmoprecipitation followed by sequencing （ChlP-sec0 is increasingly being used for genome-wide profiling of transcriptional regulation, as this technique enables dissection of the gene regulatory networks. With input as control, a variety of statistical methods have been proposed for identifying the enriched regions in the genome, i.e., the transcriptional factor binding sites and chromatin modifications. However, when there are no controls, whether peak calling is still reliable awaits systematic evaluations. To address this question, we used a Bayesian framework approach to show the effectiveness of peak calling without controls （PCWC）. Using several different types of ChlP-seq data, we demonstrated the relatively high accuracy of PCWC with less than a 5% false discovery rate （FDR）. Compared with previously published methods, e.g., the model-based analysis of ChlP-seq （MACS）, PCWC is reliable with lower FDR. Furthermore, to interpret the biological significance of the called peaks, in combination with microarray gene expression data, gene ontology annotation and subsequent motif discovery, our results indicate PCWC possesses a high efficiency. Additionally, using in silico data, only a small number of peaks were identified, suggesting the significantly low FDR for PCWC.
基金supported by the Model Animal Research Center of Nanjing University Start Fundthe Jiangsu Natural Science Foundation(BK20140600)
文摘Skeletal muscle fitness plays vital roles in human health and disease and is determined by developmental as well as physiological inputs. These inputs control and coordinate muscle fiber programs, including capacity for fuel burning, mitochondrial ATP production, and contraction. Recent studies have demonstrated crucial roles for nuclear receptors and their co-activators, and micro RNAs(mi RNAs) in the regulation of skeletal muscle energy metabolism and fiber type determination. In this review, we present recent progress in the study of nuclear receptor signaling and mi RNA networks in muscle fiber type switching. We also discuss the therapeutic potential of nuclear receptors and mi RNAs in disease states that are associated with loss of muscle fitness.
