Chiral BINOL-phosphate assembled single hexagonal nanotube in aqueous solution for confined rearrangement acceleration.

Creating microenvironments that mimic an enzyme's active site is a critical aspect of supramolecular confined catalysis. In this study, we employ the commonly used chiral 1,1'-bi-2-naphthol (BINOL) phosphates as subcomponents to construct supramolecular hollow nanotube in an aqueous medium through non-covalent intermolecular recognition and arrangement. The hexagonal nanotubular structure is characterized by various techniques, including X-ray, NMR, ESI-MS, AFM, and TEM, and is confirmed to exist in a homogeneous aqueous solution stably. The nanotube's length in solution depends on the concentration of chiral BINOL-phosphate as a monomer. Additionally, the assembled nanotube can accelerate the rate of the 3-aza-Cope rearrangement reaction by up to 85-fold due to the interior confinement effect. Based on the detailed kinetic and thermodynamic analyses, we propose that the chain-like substrates are constrained and pre-organized into a reactive chair-like conformation, which stabilizes the transition state of the reaction in the confined nanospace of the nanotube. Notably, due to the restricted conformer with less degrees of freedom, the entropic barrier is significantly reduced compared to the enthalpic barrier, resulting in a more pronounced acceleration effect.

Relationship Between DNA Methylation in Key Region and the Differential Expressions of Genes in Human Breast Tumor Tissue.

Breast cancer has a high mortality rate for females. Aberrant DNA methylation plays a crucial role in the occurrence and progression of breast carcinoma. By comparing DNA methylation differences between tumor breast tissue and normal breast tissue, we calculate and analyze the distributions of the hyper- and hypomethylation sites in different function regions. Results indicate that enhancer regions are often hypomethylated in breast cancer. CpG islands (CGIs) are mainly hypermethylated, while the flanking CGI (shores and shelves) is more easily hypomethylated. The hypomethylation in gene body region is related to the upregulation of gene expression, and the hypomethylation of enhancer regions is closely associated with gene expression upregulation in breast cancer. Some key hypomethylation sites in enhancer regions and key hypermethylation sites in CGIs for regulating key genes are, respectively, found, such as oncogenes ESR1 and ERBB2 and tumor suppressor genes FBLN2, CEBPA, and FAT4. This suggests that the recognizing methylation status of these genes will be useful for the diagnosis of breast cancer.

Predicting gene expression level by the transcription factor binding signals in human embryonic stem cells.

The transcription factor (TF) binding signals play important role in the control of gene expression. In this study, to elucidate the relationship between the transcription factor binding signals and gene expression, we firstly analyze the distributions of 57 kinds of TFs' binding signals in human H1 embryonic stem cells. Their distributions in highly and lowly expressed genes are further compared. On this basis, a statistic model of predicting gene expression level is constructed by using 57 kinds of transcription factor synthetic indexes (TFSIs). Then, the TF's Down-regulated and Up-regulated genes are predicted and the statistics significance is estimated by one-sided Kolmogorov-Smirnov test. Based on the stepwise regression analysis, the "optimal" TFSIs are selected out, and the better results for predicting the expression level of genes with high CpG content promoters (HCPs) and low CpG content promoters (LCPs) are obtained.

Gene expression classification using epigenetic features and DNA sequence composition in the human embryonic stem cell line H1.

Epigenetic factors are known to correlate with gene expression in the existing studies. However, quantitative models that accurately classify the highly and lowly expressed genes based on epigenetic factors are currently lacking. In this study, a new machine learning method combines histone modifications, DNA methylation, DNA accessibility, transcription factors, and trinucleotide composition with support vector machines (SVM) is developed in the context of human embryonic stem cell line (H1). The results indicate that the predictive accuracy will be markedly improved when the epigenetic features are considered. The predictive accuracy and Matthews correlation coefficient of the best model are as high as 95.96% and 0.92 for 10-fold cross-validation test, and 95.58% and 0.92 for independent dataset test, respectively. Our model provides a good way to judge a gene is either highly or lowly expressed gene by using genetic and epigenetic data, when the expression data of the gene is lacking. And a web-server GECES for our analysis method is established at http://202.207.14.87:8032/fuwu/GECES/index.asp, so that other scientists can easily get their desired results by our web-server, without going through the mathematical details.

Association analysis between the distributions of histone modifications and gene expression in the human embryonic stem cell.

It is well known that histone modifications are associated with gene expression. In order to further study this relationship, 16 kinds of Chip-seq histone modification data and mRNA-seq data of the human embryonic stem cell H1 are chosen. The distributions of histone modifications in the regions flanking transcription start sites (TSSs) for highly expressed and lowly expressed genes are computed, respectively. And four types of distributions of histone modifications in regions flanking TSSs and the spatial patterning of the correlations between histone modifications and gene expression are detected. Our results suggest that the correlations between the regions overlapped by peaks are higher than the non-overlapped ones for each histone modification. In addition, to obtain the effect of the cooperative action of histone modification on gene expression, five histone modification clusters are found in highly expressed and lowly expressed genes, histone modification and gene expression interaction network is constructed. To further explore which region is the main target region for the specific histone modification, the human genes are divided into five functional regions. The results indicate that histone modifications are mostly located in the promoters of highly expressed genes versus the exons of lowly expressed genes, and exons have a smaller range of normalized tag counts than other gene elements in the two groups of genes. Finally, the type specificity and regional bias of histone modifications for 11 key transcription factor genes regulating the stem cell renewal are analyzed.

Discrimination of membrane transporter protein types using K-nearest neighbor method derived from the similarity distance of total diversity measure.

Membrane transporters play crucial roles in the fundamental cellular processes of living organisms. Computational techniques are very necessary to annotate the transporter functions. In this study, a multi-class K nearest neighbor classifier based on the increment of diversity (KNN-ID) was developed to discriminate the membrane transporter types when the increment of diversity (ID) was introduced as one of the novel similarity distances. Comparisons with multiple recently published methods showed that the proposed KNN-ID method outperformed the other methods, obtaining more than 20% improvement for overall accuracy. The overall prediction accuracy reached was 83.1%, when the K was selected as 2. The prediction sensitivity achieved 76.7%, 89.1%, 80.1% for channels/pores, electrochemical potential-driven transporters, primary active transporters, respectively. Discrimination and comparison between any two different classes of transporters further demonstrated that the proposed method is a potential classifier and will play a complementary role for facilitating the functional assignment of transporters.

[Effect of Gli1 gene silencing on proliferation of K562 cells and its mechanisms].

OBJECTIVE: To investigate the effect of Gli1 gene silencing by RNA interference (RNAi) on proliferation of K562 cells and its mechanisms. METHODS: The small interference RNA (siRNA) was synthesized in vitro. K562 cells were transfected with Gli1 siRNA by the way of lipofection (lipofectamine 2000). Non-specific siRNA transfected cells were used as control. Transfection efficiencies of different siRNA concentrations were detected by flow cytometry and the best siRNA concentration was selected. The silencing effect of siRNA was demonstrated by real time PCR and Westem blot analysis. Cell proliferation was measured by MTT method, cell cycle by PI assay, c-myc and p21 mRNA level was detected by real time PCR analysis. RESULTS: Transfection efficiency of siRNA was increased in a dose-dependent manner when siRNA concentration was below 200 pmol, and the highest transfection efficiency reached (80.11 ± 5.63)%. Both the mRNA and protein level of Gli1 was down-regulated in Gli1 specific siRNA group, the mRNA level was (52.60 ± 3.57)% of that of control group after 24 h (t = 20.33, P < 0.01) and the protein level was (79.31 ± 5.58)% of that of control group after 48 h (t = 6.54, P < 0.01). The cell proliferation rate in Gli1 siRNA group was (94.41 ± 3.58)% (t = 2.40, P = 0.05) and (90.22 ± 3.34)% (t = 4.37, P < 0.01) of that of control group after 24 h and 48 h, respectively. G(2)/M cell cycle arrest was observed, the mRNA level of c-myc was down-regulated while p21 was up-regulated in Gli1 siRNA group after 24 h and 48 h (P < 0.05). CONCLUSIONS: Targeted silencing of Gli1 gene by RNAi inhibits the proliferation of K562 cells, which acts through the down-regulation of c-myc and up-regulation of p21 expression.