ORCID Profile
0000-0003-1516-879X
Current Organisation
IT University of Copenhagen
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Publisher: Frontiers Media SA
Date: 03-07-2020
Publisher: Springer Science and Business Media LLC
Date: 03-2014
DOI: 10.1038/NATURE12787
Publisher: Oxford University Press (OUP)
Date: 2016
Abstract: Genomics consortia have produced large datasets profiling the expression of genes, micro-RNAs, enhancers and more across human tissues or cells. There is a need for intuitive tools to select subsets of such data that is the most relevant for specific studies. To this end, we present SlideBase, a web tool which offers a new way of selecting genes, promoters, enhancers and microRNAs that are preferentially expressed/used in a specified set of cells/tissues, based on the use of interactive sliders. With the help of sliders, SlideBase enables users to define custom expression thresholds for in idual cell types/tissues, producing sets of genes, enhancers etc. which satisfy these constraints. Changes in slider settings result in simultaneous changes in the selected sets, updated in real time. SlideBase is linked to major databases from genomics consortia, including FANTOM, GTEx, The Human Protein Atlas and BioGPS. Database URL: slidebase.binf.ku.dk
Publisher: American Diabetes Association
Date: 11-2016
DOI: 10.2337/DB16-0631
Abstract: White adipose tissue (WAT) can develop into several phenotypes with different pathophysiological impact on type 2 diabetes. To better understand the adipogenic process, the transcriptional events that occur during in vitro differentiation of human adipocytes were investigated and the findings linked to WAT phenotypes. Single-molecule transcriptional profiling provided a detailed map of the expressional changes of genes, enhancers, and long noncoding RNAs, where different types of transcripts share common dynamics during differentiation. Common signatures include early downregulated, transient, and late induced transcripts, all of which are linked to distinct developmental processes during adipogenesis. Enhancers expressed during adipogenesis overlap significantly with genetic variants associated with WAT distribution. Transiently expressed and late induced genes are associated with hypertrophic WAT (few but large fat cells), a phenotype closely linked to insulin resistance and type 2 diabetes. Transcription factors that are expressed early or transiently affect differentiation and adipocyte function and are controlled by several well-known upstream regulators such as glucocorticosteroids, insulin, cAMP, and thyroid hormones. Taken together, our results suggest a complex but highly coordinated regulation of adipogenesis.
Publisher: American Society of Hematology
Date: 24-04-2014
DOI: 10.1182/BLOOD-2013-02-482893
Abstract: In granulopoiesis, changes in DNA methylation preferably occur at points of lineage restriction in low CpG areas. DNA methylation is dynamic in enhancer elements and appears to regulate the expression of key transcription factors and neutrophil genes.
Publisher: Cold Spring Harbor Laboratory
Date: 07-2020
Abstract: Gene expression profiles in homologous tissues have been observed to be different between species, which may be due to differences between species in the gene expression program in each cell type, but may also reflect differences in cell type composition of each tissue in different species. Here, we compare expression profiles in matching primary cells in human, mouse, rat, dog, and chicken using Cap Analysis Gene Expression (CAGE) and short RNA (sRNA) sequencing data from FANTOM5. While we find that expression profiles of orthologous genes in different species are highly correlated across cell types, in each cell type many genes were differentially expressed between species. Expression of genes with products involved in transcription, RNA processing, and transcriptional regulation was more likely to be conserved, while expression of genes encoding proteins involved in intercellular communication was more likely to have erged during evolution. Conservation of expression correlated positively with the evolutionary age of genes, suggesting that ergence in expression levels of genes critical for cell function was restricted during evolution. Motif activity analysis showed that both promoters and enhancers are activated by the same transcription factors in different species. An analysis of expression levels of mature miRNAs and of primary miRNAs identified by CAGE revealed that evolutionary old miRNAs are more likely to have conserved expression patterns than young miRNAs. We conclude that key aspects of the regulatory network are conserved, while differential expression of genes involved in cell-to-cell communication may contribute greatly to phenotypic differences between species.
Publisher: Springer Science and Business Media LLC
Date: 03-2014
DOI: 10.1038/NATURE13182
Publisher: American Association for the Advancement of Science (AAAS)
Date: 27-02-2015
Abstract: In order to understand cellular differentiation, it is important to understand the timing of the regulation of gene expression. Arner et al. used cap analysis of gene expression (CAGE) to analyze gene enhancer and promoter activities in a number of human and mouse cell types. The RNA of enhancers was transcribed first, followed by that of transcription factors, and finally by genes that are not transcription factors. Science , this issue p. 1010
Publisher: Cold Spring Harbor Laboratory
Date: 19-12-2016
DOI: 10.1101/095349
Abstract: Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share patterns of transcriptional regulation. Accordingly, shared transcriptional regulation (coexpression) may help prioritise loci associated with a given trait, and help to identify the biological processes underlying it. Using cap analysis of gene expression (CAGE) profiles of promoter and enhancer-derived RNAs across 1824 human s les, we have quantified coexpression of RNAs originating from trait-associated regulatory regions using a novel analytical method (network density analysis NDA). For most traits studied, sequence variants in regulatory regions were linked to tightly coexpressed networks that are likely to share important functional characteristics. These networks implicate particular cell types and tissues in disease pathogenesis for ex le, variants associated with ulcerative colitis are linked to expression in gut tissue, whereas Crohn’s disease variants are restricted to immune cells. We show that this coexpression signal provides additional independent information for fine mapping likely causative variants. This approach identifies additional genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. This approach enables a deeper biological understanding of the causal basis of complex traits. We discover that variants associated with a specific disease share expression profiles across tissues and cell types, enabling fine mapping and identification of new disease-associated variants, illuminating key cell types involved in disease pathogenesis.
Publisher: Cold Spring Harbor Laboratory
Date: 30-07-2015
Abstract: Promoters are central to the regulation of gene expression. Changes in gene regulation are thought to underlie much of the adaptive ersification between species and phenotypic variation within populations. In contrast to earlier work emphasizing the importance of enhancer evolution and subtle sequence changes at promoters, we show that dramatic changes such as the complete gain and loss (collectively, turnover) of functional promoters are common. Using quantitative measures of transcription initiation in both humans and mice across 52 matched tissues, we discriminate promoter sequence gains from losses and resolve the lineage of changes. We also identify expression ergence and functional turnover between orthologous promoters, finding only the latter is associated with local sequence changes. Promoter turnover has occurred at the majority ( %) of protein-coding genes since humans and mice erged. Tissue-restricted promoters are the most evolutionarily volatile where retrotransposition is an important, but not the sole, source of innovation. There is considerable heterogeneity of turnover rates between promoters in different tissues, but the consistency of these in both lineages suggests that the same biological systems are similarly inclined to transcriptional rewiring. The genes affected by promoter turnover show evidence of adaptive evolution. In mice, promoters are primarily lost through deletion of the promoter containing sequence, whereas in humans, many promoters appear to be gradually decaying with weak transcriptional output and relaxed selective constraint. Our results suggest that promoter gain and loss is an important process in the evolutionary rewiring of gene regulation and may be a significant source of phenotypic ersification.
Publisher: Public Library of Science (PLoS)
Date: 03-2018
Publisher: Springer Science and Business Media LLC
Date: 12-2014
Publisher: Springer Science and Business Media LLC
Date: 28-04-2014
DOI: 10.1038/NG.2965
Abstract: The importance of microRNAs and long noncoding RNAs in the regulation of pluripotency has been documented however, the noncoding components of stem cell gene networks remain largely unknown. Here we investigate the role of noncoding RNAs in the pluripotent state, with particular emphasis on nuclear and retrotransposon-derived transcripts. We have performed deep profiling of the nuclear and cytoplasmic transcriptomes of human and mouse stem cells, identifying a class of previously undetected stem cell-specific transcripts. We show that long terminal repeat (LTR)-derived transcripts contribute extensively to the complexity of the stem cell nuclear transcriptome. Some LTR-derived transcripts are associated with enhancer regions and are likely to be involved in the maintenance of pluripotency.
No related grants have been discovered for Robin Andersson.