Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation

Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIAPET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intragenic, extragenic, and intergenic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions. Most genes with promoter-promoter interactions were active and transcribed cooperatively, and some interacting promoters could influence each other implying combinatorial complexity of transcriptional controls. Comparative analyses of different cell lines showed that cell-specific chromatin interactions could provide structural frameworks for cell-specific transcription, and suggested significant enrichment of enhancer-promoter interactions for cell-specific functions. Furthermore, genetically-identified disease-associated noncoding elements were found to be spatially engaged with corresponding genes through long-range interactions. Overall, our study provides insights into transcription regulation by three-dimensional chromatin interactions for both housekeeping and cell-specific genes in human cells

Technical review on crumb rubber drying process and the potential of advanced drying technique

Intensive thermal energy and extensive drying period are required in rubber drying process due to its low conductivity and dielectric properties. Thus, selection of advanced drying techniques of crumbs rubber is essential for the sake of efficiency and energy conservation. The integration of advanced dryers ranging from electromagnetic heater, fluidized bed dryer, heat pump and the vacuum environment were discussed in details in paper. In summary, cost and energy efficient dryer is the aim of this research work and it is important that this technology offers a robust and reliable solution to the rubber processing industry

Dynamic changes in the human methylome during differentiation

DNA methylation is a critical epigenetic regulator in mammalian development. Here, we present a whole-genome comparative view of DNA methylation using bisulfite sequencing of three cultured cell types representing progressive stages of differentiation: human embryonic stem cells (hESCs), a fibroblastic differentiated derivative of the hESCs, and neonatal fibroblasts. As a reference, we compared our maps with a methylome map of a fully differentiated adult cell type, mature peripheral blood mononuclear cells (monocytes). We observed many notable common and cell-type-specific features among all cell types. Promoter hypomethylation (both CG and CA) and higher levels of gene body methylation were positively correlated with transcription in all cell types. Exons were more highly methylated than introns, and sharp transitions of methylation occurred at exon–intron boundaries, suggesting a role for differential methylation in transcript splicing. Developmental stage was reflected in both the level of global methylation and extent of non-CpG methylation, with hESC highest, fibroblasts intermediate, and monocytes lowest. Differentiation-associated differential methylation profiles were observed for developmentally regulated genes, including the HOX clusters, other homeobox transcription factors, and pluripotence-associated genes such as POU5F1, TCF3, and KLF4. Our results highlight the value of high-resolution methylation maps, in conjunction with other systems-level analyses, for investigation of previously undetectable developmental regulatory mechanisms

Impacts of different drying strategies on drying characteristics, the retention of bio-active ingredient and colour changes of dried Roselle

The drying kinetics of Roselle (Hibiscus sabdariffa L.) of variety Terengganu (UMKL-1) and the quality attribution of Roselle were studied. The experiments were conducted using four different drying methods, including solar greenhouse drying (SD), solar greenhouse with intermittent heat pump drying (SIHP), hot air drying (HA) and heat pump drying (HP). Among the four drying methods, HP achieved the highest drying rate at a range from 0.054 g H2O·(g DM)− 1·min− 1 to 0.212 g H2O·(g DM)− 1·min− 1 while SD had the lowest drying rate, measured at 0.042 g H2O·(g DM)− 1·min− 1. The analysis on colour kinetics revealed that there is no significant colour loss (p > 0.05) observed from HP's dried Roselle. Greater amount of flavonoid compounds i.e. protocatechuic acid was found in SD and SIHP dried finished product whereas HP's dried Roselle contains higher percentage of catechin as compared to other drying methods

RNA at the epicentre of human development

The engineering of skeletal muscle requires platforms that facilitate the proliferation and maintenance of primary muscle stem cells (myoblasts) and muscle fibre maturation in a manner that reflects native muscle structure. We have been investigating the use of nanostructured conducting polymer surfaces for the orientation and electrical stimulation of cells and tissues and have developed a hybrid conducting polymer and carbon nanotube plaform, suitable for ex vivo muscle growth, differentiation and electrical stimulation. In this study, Carbon nanotube fibres were laid down in parallel on gold coated mylar. Layers of polypyrrole (doped with pTS) were galvinostatically grown over the carbon nanotube fibre mats to create a nanostructured polypyrrole surface. Myoblasts extracted from 8 week old mice were seeded onto polymer platforms and induced to differentiate into myotubes. Analysis of myofibre differentiation and orientation was then performed. In addition, total RNA was harvested from myotubes that had undergone bipolar electrical stimulation on the platforms 8 hours a day, for 3 days. Whole genome arrays (Codelink) were then used to assess gene expression changes in the electrically stimulated myotubes. Platforms were developed to encourage the alignment and differentiation of skeletal muscle stem cells (myoblasts) to reflect the orientation of mature skeletal muscle. Nanostructured platforms were created by orientation of carbon nanotube fibres on a conducting gold mylar surface, over which a layers of conductive polypyrrole were deposited. Human and murine myoblasts could be grown and differentiated on these platforms without the use of cell adhesion molecules. A significant increase in myotube orientation was seen on nanostructured surfaces, i.e. polypyrrole films with an underlying layer of orientated carbon nanotube fibres. This orientation decreased with increasing thickness of the polypyrrole, suggesting a strong influence of the nanostructure on the orientation of myofibres. In addition, a significant number of gene expression changes were detected in myofibres electrically stimulated on the platforms. A number of these genes were associated with muscle differentiation and myoblast fusion, demonstrating that these platforms can be used to influence the differentiation state of skeletal myoblasts through electrical stimulation. These studies demonstrate that novel hybrid platforms can be used to influence skeletal muscle differentiation ex vivo, through electrical stimulation. In addition these platforms can influence muscle fibre orientation in a manner reflecting the in vivo architecture of the parent tissue. Such platforms have application for controlling the regeneration of skeletal muscle in vivo and for the integration of bionic devices designed to facilitate muscle regeneration and function

Interdomain interaction of Stat3 regulates its Src homology 2 domain-mediated receptor binding activity

10.1074/jbc.M105525200Journal of Biological Chemistry2772017556-17563JBCH

An integrative model of pathway convergence in genetically heterogeneous blast crisis chronic myeloid leukemia

Targeted therapies against the BCR-ABL1 kinase have revolutionized treatment of chronic phase (CP) chronic myeloid leukemia (CML). In contrast, management of blast crisis (BC) CML remains challenging because BC cells acquire complex molecular alterations that confer stemness features to progenitor populations and resistance to BCR-ABL1 tyrosine kinase inhibitors. Comprehensive models of BC transformation have proved elusive because of the rarity and genetic heterogeneity of BC, but are important for developing biomarkers predicting BC progression and effective therapies. To better understand BC, we performed an integrated multiomics analysis of 74 CP and BC samples using wholegenome and exome sequencing, transcriptome and methylome profiling, and chromatin immunoprecipitation followed by high-throughput sequencing. Employing pathway-based analysis, we found the BC genome was significantly enriched for mutations affecting components of the polycomb repressive complex (PRC) pathway. While transcriptomically, BC progenitors were enriched and depleted for PRC1- and PRC2-related gene sets respectively. By integrating our data sets, we determined that BC progenitors undergo PRCdriven epigenetic reprogramming toward a convergent transcriptomic state. Specifically, PRC2 directs BC DNA hypermethylation, which in turn silences key genes involved in myeloid differentiation and tumor suppressor function via so-called epigenetic switching, whereas PRC1 represses an overlapping and distinct set of genes, including novel BC tumor suppressors. On the basis of these observations, we developed an integrated model of BC that facilitated the identification of combinatorial therapies capable of reversing BC reprogramming (decitabine1PRC1 inhibitors), novel PRC-silenced tumor suppressor genes (NR4A2), and gene expression signatures predictive of disease progression and drug resistance in CP