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SM08 Programme
SATELLITE MEETING Regulation of gene expression from a distance: exploring mechanisms The Royal Society at Chicheley Hall, home of the Kavli Royal Society International Centre Organised by Professor Wendy Bickmore and Professor Veronica van Heyningen FRS Wednesday 24 – Thursday 25 October 2012 DAY 1 DAY 2 SESSION 1 SESSION 2 SESSION 3 SESSION 4 Enhancer assays Quantitative and dynamic analysis Quantitative & dynamic analysis of Defining enhancers and their mechanisms – transgenes, genetics, and interactomes of transcription protein binding at regulatory of action Chair: Professor Nick Hastie CBE FRS Chair: elements Chair: Dr Duncan Odom Welcome by RS & lead 09.00 Professor Anne Ferguson-Smith Chair: Professor Constance Bonifer organiser The evolution of global Dynamic use of enhancers in Design rules for bacterial Massively parallel functional 09.05 enhancers 13.30 development 09.00 enhancers 13.15 dissection of mammalian enhancers Professor Denis Duboule Professor Mike Levine Dr Roee Amit Dr Rupali Patwardhan 09.30 Discussion 14.00 Discussion 09.30 Discussion 13.45 Discussion Complex protein dynamics at HERC2 rs12913832 modulates The pluripotent 3D genome Gene expression genomics eukaryotic regulatory human pigmentation by attenuating 09.45 14.15 09.45 Professor Wouter de Laat Dr Sarah Teichmann elements chromatin-loop formation between a 14.00 Dr Gordon Hager long-range enhancer and the OCA2 promoter 10.15 Discussion 14.45 Discussion 10.15 Discussion Dr Robert-Jan Palstra 10.30 Coffee 15.00 Tea 10.30 Coffee 14.15 Tea Maps of open chromatin -
Contents and Society
8 EMBL August 2001 &cetera Newsletter of the European Molecular Biology Laboratory published by the Office of Information and Public Affairs EMBL appoints heads for Hinxton and Monterotondo MBLhas appointed new heads of the EBI in Hinxton and the A priority for both scientists will be to boost research activities at EMouse Biology Programme in Monterotondo. Nadia their units. Past funding limitations have prevented the EBI from Rosenthal, Associate Professor at Harvard and consulting editor developing a full research programme, although there have been at the New England Journal of Medicine, has taken charge of the a few very active groups since the site was opened. New funds Mouse Biology Programme, assuming the post vacated by Klaus from the EMBL member states will permit the addition of a full Rajewsky in June. Janet Thornton, Professor at the University complement of research teams, just as Cameron and his col- College of London and Fellow of the Royal Society, will direct leagues have been extremely successful in obtaining major fund- activities at the EBI, especially research. She succeeds Michael ing from the EC and the Wellcome Trust to bolster the EBI data- Ashburner, who has served as Co-Head of the Institute alongside bases and related services. Graham Cameron since the EBI was launched five years ago. Monterotondo, which opened in 1999, has been waiting for the "The new five-year scientific plan at EMBL stresses functional g reen light from EMBL's Council to reach critical mass. genomics and foresees substantial expansion of the EBI and the Rosenthal’s appointment comes at a time when a partner on the Mouse Biology Programme at Monterotondo," says Director Monterotondo campus, the European Mutant Mouse Archive General Fotis C. -
High-Resolution Mapping of Transcriptional Dynamics Across Tissue Development Reveals a Stable Mrna–Trna Interface
Downloaded from genome.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Research High-resolution mapping of transcriptional dynamics across tissue development reveals a stable mRNA–tRNA interface Bianca M. Schmitt,1,5 Konrad L.M. Rudolph,2,5 Panagiota Karagianni,3 Nuno A. Fonseca,2 Robert J. White,4 Iannis Talianidis,3 Duncan T. Odom,1 John C. Marioni,2 and Claudia Kutter1 1University of Cambridge, Cancer Research UK Cambridge Institute, Cambridge, CB2 0RE, United Kingdom; 2European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom; 3B.S.R.C. Alexander Flemming, 16672, Vari, Athens, Greece; 4University of York, Department of Biology, Heslington, York, YO10 5DD, United Kingdom The genetic code is an abstraction of how mRNA codons and tRNA anticodons molecularly interact during protein synthesis; the stability and regulation of this interaction remains largely unexplored. Here, we characterized the expression of mRNA and tRNA genes quantitatively at multiple time points in two developing mouse tissues. We dis- covered that mRNA codon pools are highly stable over development and simply reflect the genomic background; in contrast, precise regulation of tRNA gene families is required to create the corresponding tRNA transcriptomes. The dynamic regulation of tRNA genes during development is controlled in order to generate an anticodon pool that closely corresponds to messenger RNAs. Thus, across development, the pools of mRNA codons and tRNA anticodons are invariant and highly correlated, revealing a stable molecular interaction interlocking transcription and translation. [Supplemental material is available for this article.] Transcription of the mammalian genome is divided among mul- differencesinexpressionofspecifictRNAgenesmaycontribute tiple RNA polymerases (Pol), each transcribing a nonoverlapping to tumorigenesis by favoring translation of cancer-promoting set of genes. -
EMBO Facts & Figures
excellence in life sciences Reykjavik Helsinki Oslo Stockholm Tallinn EMBO facts & figures & EMBO facts Copenhagen Dublin Amsterdam Berlin Warsaw London Brussels Prague Luxembourg Paris Vienna Bratislava Budapest Bern Ljubljana Zagreb Rome Madrid Ankara Lisbon Athens Jerusalem EMBO facts & figures HIGHLIGHTS CONTACT EMBO & EMBC EMBO Long-Term Fellowships Five Advanced Fellows are selected (page ). Long-Term and Short-Term Fellowships are awarded. The Fellows’ EMBO Young Investigators Meeting is held in Heidelberg in June . EMBO Installation Grants New EMBO Members & EMBO elects new members (page ), selects Young EMBO Women in Science Young Investigators Investigators (page ) and eight Installation Grantees Gerlind Wallon EMBO Scientific Publications (page ). Programme Manager Bernd Pulverer S Maria Leptin Deputy Director Head A EMBO Science Policy Issues report on quotas in academia to assure gender balance. R EMBO Director + + A Conducts workshops on emerging biotechnologies and on H T cognitive genomics. Gives invited talks at US National Academy E IC of Sciences, International Summit on Human Genome Editing, I H 5 D MAN 201 O N Washington, DC.; World Congress on Research Integrity, Rio de A M Janeiro; International Scienti c Advisory Board for the Centre for Eilish Craddock IT 2 015 Mammalian Synthetic Biology, Edinburgh. Personal Assistant to EMBO Fellowships EMBO Scientific Publications EMBO Gold Medal Sarah Teichmann and Ido Amit receive the EMBO Gold the EMBO Director David del Álamo Thomas Lemberger Medal (page ). + Programme Manager Deputy Head EMBO Global Activities India and Singapore sign agreements to become EMBC Associate + + Member States. EMBO Courses & Workshops More than , participants from countries attend 6th scienti c events (page ); participants attend EMBO Laboratory Management Courses (page ); rst online course EMBO Courses & Workshops recorded in collaboration with iBiology. -
Peakmatcher: Matching Peaks Across Genome Assemblies
PeakMatcher: Matching Peaks Across Genome Assemblies Ronald J. Nowling Christopher R. Beal Scott Emrich Milwaukee School of Engineering Marquette University University of Tennessee–Knoxville Milwaukee, Wisconsin Milwaukee, Wisconsin Knoxville, Tennessee [email protected] [email protected] [email protected] Susanta K. Behura Marc S. Halfon Molly Duman-Scheel University of Missouri SUNY at Buffalo Indiana University School of Medicine Columbia, Missouri Buffalo, New York South Bend, Indiana [email protected] [email protected] [email protected] ABSTRACT The second data set was STARR-Seq (Self-Transcribing Active When reference genome assemblies are updated, the peaks from Regulatory Region Sequencing) of Drosophila melanogaster DNA DNA enrichment assays such as ChIP-Seq and FAIRE-Seq need in S2 culture cells [1]. We called STARR peaks against two versions to be called again using the new genome assembly. PeakMatcher (dm3 and r5.53) of the D. melanogaster genome [6]. PeakMatcher is an open-source package that aids in validation by matching matched 77.4% (precision) of the 4,195 dm3 peaks with 94.8% (recall) peaks across two genome assemblies using the alignment of reads of the 3,114 r5.53 peaks. or within the same genome. PeakMatcher calculates recall and PeakMatcher and associated documentation are available on precision while also outputting lists of peak-to-peak matches. GitHub (https://github.com/rnowling/peak-matcher) under the open- PeakMatcher uses read alignments to match peaks across genome source Apache Software License v2. PeakMatcher was written in assemblies. PeakMatcher finds all read aligned to one genome that Python 3 using the intervaltree library. -
DKFZ Postdoctoral Fellowships 2021 Hosting Group Information For
DKFZ Postdoctoral Fellowships 2021 Hosting group information for applicants Name of DKFZ research division/group: Division of Regulatory Genomics and Cancer Evolution (B270) Contact person: Duncan Odom Group homepage: https://www.dkfz.de/en/regulatorische-genomik/index.php Please visit our website for further information on our research and recent publications. RESEARCH PROFILE AND PROJECT TOPICS: Dr Odom’s laboratory studies how genetic sequence information shapes the cell's DNA regulatory landscape and thus the trajectory of cancer genome evolution. Our long-standing interest in interspecies analysis of matched functional genomic data has revealed the extensive and rapid turn-over of tissue-specific transcription factor binding, insulator elements, polymerase occupancies, and enhancer activities during organismal evolution. My laboratory has begun exploiting single-cell RNA-sequencing and large-scale whole genome sequencing in understanding molecular and cancer genome evolution. Recent high-profile studies from the Odom lab used single-cell transcriptional analysis to conclusively demonstrate that ageing results in substantial increases in cell-to-cell transcriptional variability and exploited chemical carcinogenesis in mouse liver to reveal how the persistence of DNA lesions profoundly shapes tumour genomes. First, we are currently interviewing for experimentally focused postdoctoral fellows to spearhead multiple diverse and interdisciplinary collaborations in single-cell analysis, functional genomics, and spatial transcriptomics with Gerstung, Stegle, Hoefer, and Goncalves laboratories at DKFZ. Such an appointment would offer unusual opportunities for an experimentally-focused postdoc to learn and deploy bioinformatics tools in collaboration with one or more world-leading computational biology laboratories. Second, we are seeking a postdoctoral researcher to spearhead a collaboration with Edith Heard's group at EMBL, focused on how X-chromosome dynamics can shape disease susceptibility in older individuals. -
Paterson Institute for Cancer Research Scientific Report 2008 Contents
paterson institute for cancer research scientific report 2008 cover images: Main image supplied by Karim Labib and Alberto sanchez-Diaz (cell cycle Group). Budding yeast cells lacking the inn1 protein are unable to complete cytokinesis. these cells express a fusion of a green fluorescent protein to a marker of the plasma membrane, and have red fluorescent proteins attached to components of the spindle poles and actomyosin ring (sanchez-Diaz et al., nature cell Biology 2008; 10: 395). Additional images: front cover image supplied by Helen rushton, simon Woodcock and Angeliki Malliri (cell signalling Group). the image is of a mitotic spindle in fixed MDcK (Madin-Darby canine kidney) epithelial cells, which have been stained with an anti-beta tubulin antibody (green), DApi (blue) and an anti-centromere antibody (crest, red) which recognises the kinetochores of the chromosomes. the image was taken on the spinning disk confocal microscope using a 150 x lens. rear cover image supplied by Andrei ivanov and tim illidge (targeted therapy Group). Visualisation of tubulin (green) and quadripolar mitosis (DnA stained with DApi), Burkitt’s lymphoma namalwa cell after 10 Gy irradiation. issn 1740-4525 copyright 2008 © cancer research UK Paterson Institute for Cancer Research Scientific Report 2008 Contents 4 Director’s Introduction Researchers’ pages – Paterson Institute for Cancer Research 8 Crispin Miller Applied Computational Biology and Bioinformatics 10 Geoff Margison Carcinogenesis 12 Karim Labib Cell Cycle 14 Iain Hagan Cell Division 16 Nic Jones -
Register of Declared Private, Professional Commercial and Other Interests
REGISTER OF DECLARED PRIVATE, PROFESSIONAL COMMERCIAL AND OTHER INTERESTS Please refer to the attached guidance notes before completing this register entry. In addition to guidance on each section, examples of information required are also provided. Where you have no relevant interests in the relevant category, please enter ‘none’ in the register entry. Name: Michaela Frye Please list all MRC bodies you are a member of: E.g. Council, Strategy Board, Research Board, Expert Panel etc and your position (e.g. chair, member). Regenerative Medicine Research Committee member Main form of employment: Name of University and Department or other employing body (include location), and your position. University of Cambridge, Department of Genetics, Cancer Research UK Senior Fellow Research group/department web page: Provide a link to any relevant web pages for your research group or individual page on your organisation’s web site. http://www.stemcells.cam.ac.uk/research/affiliates/dr-frye http://www.gen.cam.ac.uk/research-groups/frye Please give details of any potential conflicts of interests arising out of the following: 1. Personal Remuneration: Including employment, pensions, consultancies, directorships, honoraria. See section 1 for further guidance. None 2. Shareholdings and Financial Interests in companies: Include the names of companies involved in medical/biomedical research, pharmaceuticals, biotechnology, healthcare provision and related fields where shareholdings or other financial interests. See section 2 for thresholds and further guidance. None 3. Research Income during current session (financial year) : Declare all research income from bodies supported by the MRC and research income from other sources above the limit of £50k per grant for the year. -
Transcription Factor Binding Cells and Their Progeny
RESEARCH HIGHLIGHTS knock-in alleles at the Lgr6 locus, allowing them to visualize Lgr6+ Transcription factor binding cells and their progeny. Shortly after birth, Lgr6 expression in the skin becomes restricted, eventually marking a unique population located at Most transcription factor binding events differ between closely the central isthmus just above the bulge region in resting hair follicles. related species despite conservation of functional targets. Now, Paul Flicek and Duncan Odom and colleagues report an Through a series of lineage-tracing studies in adult mice, they showed + evolutionary comparison of transcription factor CEBPA binding that the progeny of Lgr6 cells contribute not only to hair follicles but among five vertebrate species (Science published online, also to sebaceous glands and interfollicular epidermis. They also showed + doi:10.1126/science.1186176, 8 April 2010). The authors that transplanted Lgr6 stem cells could reconstitute fully formed hair compared genome-wide binding of CEBPA as determined by follicles and contribute to all three lineages in host skin. Finally, they + ChIP-sequencing in livers of human, mouse, dog, short-tailed showed that Lgr6 cells contribute to wound healing. These findings opossum and chicken. The CEBPA binding motif was virtually identify Lgr6 as a marker of a distinct epidermal stem cell population identical between the five species, but most binding events contributing to all three skin lineages. KV were species-specific. Only 10% to 22% of binding events were shared between any two placental mammals, and there was even greater divergence of binding events in opossum and chicken. Identifying nonobvious phenologs Only 35 binding events were shared by all five species. -
Functional Assessment of Human Enhancer Activities Using Whole-Genome STARR- Sequencing Yuwen Liu1,2†, Shan Yu1,2†, Vineet K
Liu et al. Genome Biology (2017) 18:219 DOI 10.1186/s13059-017-1345-5 RESEARCH Open Access Functional assessment of human enhancer activities using whole-genome STARR- sequencing Yuwen Liu1,2†, Shan Yu1,2†, Vineet K. Dhiman1,2†, Tonya Brunetti1,2, Heather Eckart2 and Kevin P. White1,2,3* Abstract Background: Genome-wide quantification of enhancer activity in the human genome has proven to be a challenging problem. Recent efforts have led to the development of powerful tools for enhancer quantification. However, because of genome size and complexity, these tools have yet to be applied to the whole human genome. Results: In the current study, we use a human prostate cancer cell line, LNCaP as a model to perform whole human genome STARR-seq (WHG-STARR-seq) to reliably obtain an assessment of enhancer activity. This approach builds upon previously developed STARR-seq in the fly genome and CapSTARR-seq techniques in targeted human genomic regions. With an improved library preparation strategy, our approach greatly increases the library complexity per unit of starting material, which makes it feasible and cost-effective to explore the landscape of regulatory activity in the much larger human genome. In addition to our ability to identify active, accessible enhancers located in open chromatin regions, we can also detect sequences with the potential for enhancer activity that are located in inaccessible, closed chromatin regions. When treated with the histone deacetylase inhibitor, Trichostatin A, genes nearby this latter class of enhancers are up-regulated, demonstrating the potential for endogenous functionality of these regulatory elements. Conclusion: WHG-STARR-seq provides an improved approach to current pipelines for analysis of high complexity genomes to gain a better understanding of the intricacies of transcriptional regulation. -
Decoupling of Evolutionary Changes in Transcription Factor Binding and Gene Expression in Mammals
Downloaded from genome.cshlp.org on April 13, 2016 - Published by Cold Spring Harbor Laboratory Press Research Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals Emily S. Wong,1 David Thybert,1 Bianca M. Schmitt,2 Klara Stefflova,2,4 Duncan T. Odom,2,3 and Paul Flicek1,3 1European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom; 2University of Cambridge, Cancer Research UK - Cambridge Institute, Li Ka Shing Centre, Cambridge, CB2 0RE, United Kingdom; 3Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom To understand the evolutionary dynamics between transcription factor (TF) binding and gene expression in mammals, we compared transcriptional output and the binding intensities for three tissue-specific TFs in livers from four closely related mouse species. For each transcription factor, TF-dependent genes and the TF binding sites most likely to influence mRNA expression were identified by comparing mRNA expression levels between wild-type and TF knockout mice. Independent evolution was observed genome-wide between the rate of change in TF binding and the rate of change in mRNA ex- pression across taxa, with the exception of a small number of TF-dependent genes. We also found that binding intensities are preferentially conserved near genes whose expression is dependent on the TF, and the conservation is shared among binding peaks in close proximity to each other near the TSS. Expression of TF-dependent genes typically showed an increased sensitivity to changes in binding levels as measured by mRNA abundance. -
Extensive Compensatory Cis-Trans Regulation in the Evolution of Mouse Gene Expression
Downloaded from genome.cshlp.org on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press Research Extensive compensatory cis-trans regulation in the evolution of mouse gene expression Angela Goncalves,1,5 Sarah Leigh-Brown,2,3,5 David Thybert,1,6 Klara Stefflova,3,6 Ernest Turro,2,3 Paul Flicek,1,4 Alvis Brazma,1 Duncan T. Odom,2,3,4,7 and John C. Marioni1,7 1European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, United Kingdom; 2Department of Oncology, University of Cambridge, Hills Road, Cambridge CB2 0XZ, United Kingdom; 3Cancer Research UK, Cambridge Research Institute, Robinson Way, Cambridge CB2 0RE, United Kingdom; 4Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom Gene expression levels are thought to diverge primarily via regulatory mutations in trans within species, and in cis between species. To test this hypothesis in mammals we used RNA-sequencing to measure gene expression divergence between C57BL/6J and CAST/EiJ mouse strains and allele-specific expression in their F1 progeny. We identified 535 genes with parent-of-origin specific expression patterns, although few of these showed full allelic silencing. This suggests that the number of imprinted genes in a typical mouse somatic tissue is relatively small. In the set of nonimprinted genes, 32% showed evidence of divergent expression between the two strains. Of these, 2% could be attributed purely to variants acting in trans, while 43% were attributable only to variants acting in cis. The genes with expression divergence driven by changes in trans showed significantly higher sequence constraint than genes where the divergence was explained by variants acting in cis.