Global gene expression analysis of human erythroid progenitors

This article is available open access through the publisher’s website. Copyright @ 2011 American Society of Hematology. This article has an erratum: http://bloodjournal.hematologylibrary.org/content/118/26/6993.3.Understanding the pattern of gene expression during erythropoiesis is crucial for a synthesis of erythroid developmental biology. Here, we isolated 4 distinct populations at successive erythropoietin-dependent stages of erythropoiesis, including the terminal, pyknotic stage. The transcriptome was determined using Affymetrix arrays. First, we demonstrated the importance of using defined cell populations to identify lineage and temporally specific patterns of gene expression. Cells sorted by surface expression profile not only express significantly fewer genes than unsorted cells but also demonstrate significantly greater differences in the expression levels of particular genes between stages than unsorted cells. Second, using standard software, we identified more than 1000 transcripts not previously observed to be differentially expressed during erythroid maturation, 13 of which are highly significantly terminally regulated, including RFXAP and SMARCA4. Third, using matched filtering, we identified 12 transcripts not previously reported to be continuously up-regulated in maturing human primary erythroblasts. Finally, using transcription factor binding site analysis, we identified potential transcription factors that may regulate gene expression during terminal erythropoiesis. Our stringent lists of differentially regulated and continuously expressed transcripts containing many genes with undiscovered functions in erythroblasts are a resource for future functional studies of erythropoiesis. Our Human Erythroid Maturation database is available at https://cellline.molbiol.ox.ac.uk/eryth/index.html.National Health Service Blood and Transplant, National Institute for Health Research Biomedical Research Center Program, and National Institute for Health Research

The role of chess in the development of children-parents’ perspectives

IntroductionThe study examines the role of chess in the development of children from the perspectives of parents. The research focused on analyzing the parents’ perceptions about chess’s role in their children’s development, on finding out how the perception of parents differs depending on whether they know how to play chess or not, and on outlining the profile of the parents whose children play chess.The study was conducted in Romania.MethodsIn order to conduct the study, a quantitative research method was used, while having as a research instrument a non-standardized questionnaire. The questionnaire was applied to parents of chess-playing children who are members of chess clubs from Romania. The sample of the study comprises 774 respondents.ResultsThe results of our research showed that parents are of the opinion that chess helps children develop their cognitive abilities, their character and their competitive spirit. Most of the parents focused on highlighting the positive effects of chess on the development of their children. Parents also considered that chess helped their children develop positive emotions and helped them overcome negative emotions. The results revealed differences between the opinions of parents depending on whether they know how to play chess or not. Thus, parents who do know how to play chess were more likely to focus on the positive effects of the game on the development of their children, and those who know how to play chess were also more satisfied with their children’s accumulated knowledge following chess lessons.DiscussionFindings extend our understanding of how parents perceive the way chess influences the development of their children, it offered us a perspective on the perceived benefits of chess, benefits which should be further analyzed in order to identify under what circumstances chess could be introduced in the school curriculum

Conservation of transcription factor binding events predicts gene expression across species

Recent technological advances have made it possible to determine the genome-wide binding sites of transcription factors (TFs). Comparisons across species have suggested a relatively low degree of evolutionary conservation of experimentally defined TF binding events (TFBEs). Using binding data for six different TFs in hepatocytes and embryonic stem cells from human and mouse, we demonstrate that evolutionary conservation of TFBEs within orthologous proximal promoters is closely linked to function, defined as expression of the target genes. We show that (i) there is a significantly higher degree of conservation of TFBEs when the target gene is expressed in both species; (ii) there is increased conservation of binding events for groups of TFs compared to individual TFs; and (iii) conserved TFBEs have a greater impact on the expression of their target genes than non-conserved ones. These results link conservation of structural elements (TFBEs) to conservation of function (gene expression) and suggest a higher degree of functional conservation than implied by previous studies

Human and mouse introns are linked to the same processes and functions through each genome's most frequent non-conserved motifs

We identified the most frequent, variable-length DNA sequence motifs in the human and mouse genomes and sub-selected those with multiple recurrences in the intergenic and intronic regions and at least one additional exonic instance in the corresponding genome. We discovered that these motifs have virtually no overlap with intronic sequences that are conserved between human and mouse, and thus are genome-specific. Moreover, we found that these motifs span a substantial fraction of previously uncharacterized human and mouse intronic space. Surprisingly, we found that these genome-specific motifs are over-represented in the introns of genes belonging to the same biological processes and molecular functions in both the human and mouse genomes even though the underlying sequences are not conserved between the two genomes. In fact, the processes and functions that are linked to these genome-specific sequence-motifs are distinct from the processes and functions which are associated with intronic regions that are conserved between human and mouse. The findings show that intronic regions from different genomes are linked to the same processes and functions in the absence of underlying sequence conservation. We highlight the ramifications of this observation with a concrete example that involves the microsatellite instability gene MLH1

Assembly PCR synthesis of optimally designed, compact, multi-responsive promoters suited to gene therapy application

MRC-DTA studentship award British Pharmacological Society Integrative Awar