Prof. Dr. Uwe Ohler
Profil
Forschungsthemen4
IGRK 2403/1: Analyse und Umbau des regulatorischen Genoms
Quelle ↗Förderer: DFG Graduiertenkolleg Zeitraum: 01/2019 - 12/2023 Projektleitung: Prof. Dr. Uwe Ohler
IGRK 2403: Analyse und Umbau des regulatorischen Genoms
Quelle ↗Förderer: DFG Graduiertenkolleg Zeitraum: 01/2019 - 12/2024 Projektleitung: Prof. Dr. Uwe Ohler
SFB/TRR 175/1: Von prädikativen zu mechanistischen Modellen der plastidären Genexpression mittels Hochdurchsatz-Sequenzdaten (TP D01)
Quelle ↗Förderer: DFG Sonderforschungsbereich Zeitraum: 07/2016 - 06/2021 Projektleitung: Prof. Dr. Uwe Ohler
Verbundprojekt: BZML - Berliner Zentrum für maschinelles Lernen
Quelle ↗Förderer: Bundesministerium für Forschung, Technologie und Raumfahrt Zeitraum: 08/2018 - 12/2022 Projektleitung: Prof. Dr. Uwe Ohler
Mögliche Industrie-Partner10
Stand: 26.4.2026, 19:48:44 (Top-K=20, Min-Cosine=0.4)
- 100 Treffer64.7%
- Systematic Models for Biological Systems Engineering Training NetworkP64.7%
- Systematic Models for Biological Systems Engineering Training Network
- 96 Treffer64.7%
- Systematic Models for Biological Systems Engineering Training NetworkP64.7%
- Systematic Models for Biological Systems Engineering Training Network
Protatuans-Etaireia Ereynas Viotechologias Monoprosopi Etaireia Periorisments Eythinis
P94 Treffer64.7%- Systematic Models for Biological Systems Engineering Training NetworkP64.7%
- Systematic Models for Biological Systems Engineering Training Network
- 98 Treffer64.7%
- Systematic Models for Biological Systems Engineering Training NetworkP64.7%
- Systematic Models for Biological Systems Engineering Training Network
- 94 Treffer61.2%
- Engineering of New-Generation Protein Secretion SystemsP61.2%
- Engineering of New-Generation Protein Secretion Systems
- 93 Treffer61.2%
- Engineering of New-Generation Protein Secretion SystemsP61.2%
- Engineering of New-Generation Protein Secretion Systems
- 94 Treffer61.2%
- Engineering of New-Generation Protein Secretion SystemsP61.2%
- Engineering of New-Generation Protein Secretion Systems
- 41 Treffer60.8%
- Validating C. Elegans Healthspan Model for Better Understanding Factors Causing Health and Disease, to Develop Evidence Based Prevention, Diagnostic, Therapeutic and Other StrategiesP60.8%
- Climate-smart rewilding: ecological restoration for climate change mitigation, adaptation and biodiversity support in EuropeP50.2%
- Validating C. Elegans Healthspan Model for Better Understanding Factors Causing Health and Disease, to Develop Evidence Based Prevention, Diagnostic, Therapeutic and Other Strategies
- 41 Treffer60.8%
- Validating C. Elegans Healthspan Model for Better Understanding Factors Causing Health and Disease, to Develop Evidence Based Prevention, Diagnostic, Therapeutic and Other StrategiesP60.8%
- Validating C. Elegans Healthspan Model for Better Understanding Factors Causing Health and Disease, to Develop Evidence Based Prevention, Diagnostic, Therapeutic and Other Strategies
- 41 Treffer60.8%
- Validating C. Elegans Healthspan Model for Better Understanding Factors Causing Health and Disease, to Develop Evidence Based Prevention, Diagnostic, Therapeutic and Other StrategiesP60.8%
- Validating C. Elegans Healthspan Model for Better Understanding Factors Causing Health and Disease, to Develop Evidence Based Prevention, Diagnostic, Therapeutic and Other Strategies
Publikationen25
Top 25 nach Zitationen — Quelle: OpenAlex (BAAI/bge-m3 embedded für Matching).
Science · 1192 Zitationen · DOI
Transcriptional programs that regulate development are exquisitely controlled in space and time. Elucidating these programs that underlie development is essential to understanding the acquisition of cell and tissue identity. We present microarray expression profiles of a high-resolution set of developmental time points within a single Arabidopsis root and a comprehensive map of nearly all root cell types. These cell type-specific transcriptional signatures often predict previously unknown cellular functions. A computational pipeline identified dominant expression patterns that demonstrate transcriptional similarity between disparate cell types. Dominant expression patterns along the root's longitudinal axis do not strictly correlate with previously defined developmental zones, and in many cases, we observed expression fluctuation along this axis. Both robust co-regulation of gene expression and potential phasing of gene expression were identified between individual roots. Methods that combine these profiles demonstrate transcriptionally rich and complex programs that define Arabidopsis root development in both space and time.
Nature · 728 Zitationen · DOI
Molecular Cell · 663 Zitationen · DOI
Nature · 563 Zitationen · DOI
Nature · 462 Zitationen · DOI
Genome biology · 457 Zitationen · DOI
There are relatively few recognizable binding sites for previously known general transcription factors in Drosophila core promoters. However, we identified several new motifs enriched in promoter regions. We were also able to significantly improve the performance of computational TSS prediction in Drosophila.
Genome biology · 361 Zitationen · DOI
Crosslinking and immunoprecipitation (CLIP) protocols have made it possible to identify transcriptome-wide RNA-protein interaction sites. In particular, PAR-CLIP utilizes a photoactivatable nucleoside for more efficient crosslinking. We present an approach, centered on the novel PARalyzer tool, for mapping high-confidence sites from PAR-CLIP deep-sequencing data. We show that PARalyzer delineates sites with a high signal-to-noise ratio. Motif finding identifies the sequence preferences of RNA-binding proteins, as well as seed-matches for highly expressed microRNAs when profiling Argonaute proteins. Our study describes tailored analytical methods and provides guidelines for future efforts to utilize high-throughput sequencing in RNA biology. PARalyzer is available at http://www.genome.duke.edu/labs/ohler/research/PARalyzer/.
PLoS Pathogens · 351 Zitationen · DOI
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus linked to a number of B cell cancers and lymphoproliferative disorders. During latent infection, EBV expresses 25 viral pre-microRNAs (miRNAs) and induces the expression of specific host miRNAs, such as miR-155 and miR-21, which potentially play a role in viral oncogenesis. To date, only a limited number of EBV miRNA targets have been identified; thus, the role of EBV miRNAs in viral pathogenesis and/or lymphomagenesis is not well defined. Here, we used photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) combined with deep sequencing and computational analysis to comprehensively examine the viral and cellular miRNA targetome in EBV strain B95-8-infected lymphoblastoid cell lines (LCLs). We identified 7,827 miRNA-interaction sites in 3,492 cellular 3'UTRs. 531 of these sites contained seed matches to viral miRNAs. 24 PAR-CLIP-identified miRNA:3'UTR interactions were confirmed by reporter assays. Our results reveal that EBV miRNAs predominantly target cellular transcripts during latent infection, thereby manipulating the host environment. Furthermore, targets of EBV miRNAs are involved in multiple cellular processes that are directly relevant to viral infection, including innate immunity, cell survival, and cell proliferation. Finally, we present evidence that myc-regulated host miRNAs from the miR-17/92 cluster can regulate latent viral gene expression. This comprehensive survey of the miRNA targetome in EBV-infected B cells represents a key step towards defining the functions of EBV-encoded miRNAs, and potentially, identifying novel therapeutic targets for EBV-associated malignancies.
Developmental Cell · 339 Zitationen · DOI
In all multicellular organisms, transcriptional networks orchestrate organ development. The Arabidopsis root, with its simple structure and indeterminate growth, is an ideal model for investigating the spatiotemporal transcriptional signatures underlying developmental trajectories. To map gene expression dynamics across root cell types and developmental time, we built a comprehensive, organ-scale atlas at single-cell resolution. In addition to estimating developmental progressions in pseudotime, we employed the mathematical concept of optimal transport to infer developmental trajectories and identify their underlying regulators. To demonstrate the utility of the atlas to interpret new datasets, we profiled mutants for two key transcriptional regulators at single-cell resolution, shortroot and scarecrow. We report transcriptomic and in vivo evidence for tissue trans-differentiation underlying a mixed cell identity phenotype in scarecrow. Our results support the atlas as a rich community resource for unraveling the transcriptional programs that specify and maintain cell identity to regulate spatiotemporal organ development.
Developmental Cell · 330 Zitationen · DOI
Nature Communications · 324 Zitationen · DOI
Efforts to precisely identify tumor human leukocyte antigen (HLA) bound peptides capable of mediating T cell-based tumor rejection still face important challenges. Recent studies suggest that non-canonical tumor-specific HLA peptides derived from annotated non-coding regions could elicit anti-tumor immune responses. However, sensitive and accurate mass spectrometry (MS)-based proteogenomics approaches are required to robustly identify these non-canonical peptides. We present an MS-based analytical approach that characterizes the non-canonical tumor HLA peptide repertoire, by incorporating whole exome sequencing, bulk and single-cell transcriptomics, ribosome profiling, and two MS/MS search tools in combination. This approach results in the accurate identification of hundreds of shared and tumor-specific non-canonical HLA peptides, including an immunogenic peptide derived from an open reading frame downstream of the melanoma stem cell marker gene ABCB5. These findings hold great promise for the discovery of previously unknown tumor antigens for cancer immunotherapy.
Cell Host & Microbe · 315 Zitationen · DOI
Cell Host & Microbe · 309 Zitationen · DOI
Proceedings of the National Academy of Sciences · 295 Zitationen · DOI
Understanding how the expression of transcription factor (TF) genes is modulated is essential for reconstructing gene regulatory networks. There is increasing evidence that sequences other than upstream noncoding can contribute to modulating gene expression, but how frequently they do so remains unclear. Here, we investigated the regulation of TFs expressed in a tissue-enriched manner in Arabidopsis roots. For 61 TFs, we created GFP reporter constructs driven by each TF's upstream noncoding sequence (including the 5'UTR) fused to the GFP reporter gene alone or together with the TF's coding sequence. We compared the visually detectable GFP patterns with endogenous mRNA expression patterns, as defined by a genome-wide microarray root expression map. An automated image analysis method for quantifying GFP signals in different tissues was developed and used to validate our visual comparison method. From these combined analyses, we found that (i) the upstream noncoding sequence was sufficient to recapitulate the mRNA expression pattern for 80% (35/44) of the TFs, and (ii) 25% of the TFs undergo posttranscriptional regulation via microRNA-mediated mRNA degradation (2/24) or via intercellular protein movement (6/24). The results suggest that, for Arabidopsis TFs, upstream noncoding sequences are major contributors to mRNA expression pattern establishment, but modulation of transcription factor protein expression pattern after transcription is relatively frequent. This study provides a systematic overview of regulation of TF expression at a cellular level.
Proceedings of the National Academy of Sciences · 285 Zitationen · DOI
Deep sequencing of ribosome footprints (ribosome profiling) maps and quantifies mRNA translation. Because ribosomes decode mRNA every 3 nt, the periodic property of ribosome footprints could be used to identify novel translated ORFs. However, due to the limited resolution of existing methods, the 3-nt periodicity is observed mostly in a global analysis, but not in individual transcripts. Here, we report a protocol applied to <i>Arabidopsis</i> that maps over 90% of the footprints to the main reading frame and thus offers super-resolution profiles for individual transcripts to precisely define translated regions. The resulting data not only support many annotated and predicted noncanonical translation events but also uncover small ORFs in annotated noncoding RNAs and pseudogenes. A substantial number of these unannotated ORFs are evolutionarily conserved, and some produce stable proteins. Thus, our study provides a valuable resource for plant genomics and an efficient optimization strategy for ribosome profiling in other organisms.
Genome Research · 275 Zitationen · DOI
Complex patterns of cell-type-specific gene expression are thought to be achieved by combinatorial binding of transcription factors (TFs) to sequence elements in regulatory regions. Predicting cell-type-specific expression in mammals has been hindered by the oftentimes unknown location of distal regulatory regions. To alleviate this bottleneck, we used DNase-seq data from 19 diverse human cell types to identify proximal and distal regulatory elements at genome-wide scale. Matched expression data allowed us to separate genes into classes of cell-type-specific up-regulated, down-regulated, and constitutively expressed genes. CG dinucleotide content and DNA accessibility in the promoters of these three classes of genes displayed substantial differences, highlighting the importance of including these aspects in modeling gene expression. We associated DNase I hypersensitive sites (DHSs) with genes, and trained classifiers for different expression patterns. TF sequence motif matches in DHSs provided a strong performance improvement in predicting gene expression over the typical baseline approach of using proximal promoter sequences. In particular, we achieved competitive performance when discriminating up-regulated genes from different cell types or genes up- and down-regulated under the same conditions. We identified previously known and new candidate cell-type-specific regulators. The models generated testable predictions of activating or repressive functions of regulators. DNase I footprints for these regulators were indicative of their direct binding to DNA. In summary, we successfully used information of open chromatin obtained by a single assay, DNase-seq, to address the problem of predicting cell-type-specific gene expression in mammalian organisms directly from regulatory sequence.
Nature Communications · 242 Zitationen · DOI
Recent methodological advances allowed the identification of an increasing number of RNA-binding proteins (RBPs) and their RNA-binding sites. Most of those methods rely, however, on capturing proteins associated to polyadenylated RNAs which neglects RBPs bound to non-adenylate RNA classes (tRNA, rRNA, pre-mRNA) as well as the vast majority of species that lack poly-A tails in their mRNAs (including all archea and bacteria). We have developed the Phenol Toluol extraction (PTex) protocol that does not rely on a specific RNA sequence or motif for isolation of cross-linked ribonucleoproteins (RNPs), but rather purifies them based entirely on their physicochemical properties. PTex captures RBPs that bind to RNA as short as 30 nt, RNPs directly from animal tissue and can be used to simplify complex workflows such as PAR-CLIP. Finally, we provide a global RNA-bound proteome of human HEK293 cells and the bacterium Salmonella Typhimurium.
Nature Biotechnology · 240 Zitationen · DOI
Ribosome profiling (Ribo-seq) has extended our understanding of the translational ‘vocabulary’ of the human genome, uncovering thousands of open reading frames (ORFs) within long noncoding RNAs (lncRNAs) and presumed untranslated regions (UTRs) of protein-coding genes. However, reference gene annotation projects have been circumspect in their incorporation of these ORFs because of uncertainties about their experimental reproducibility and physiological roles. Yet, it is clear that certain ‘Ribo-seq ORFs’ make stable proteins, others mediate gene regulation, and many have medical implications. Ultimately, the absence of standardized ORF annotation has created a circular problem: while Ribo-seq ORFs remain unrecognized by reference annotation databases, this lack of recognition will thwart studies examining their roles. Here, we outline a community-led effort involving Ensembl/GENCODE, the HUGO Gene Nomenclature Committee (HGNC), UniProtKB, HUPO/HPP and PeptideAtlas to produce a standardized catalog of 7,264 human Ribo-seq ORFs; a path to bring protein-level evidence for Ribo-seq ORFs into reference annotation databases; and a roadmap to facilitate research in the global community.
Nature Communications · 227 Zitationen · DOI
Protein subcellular localization is fundamental to the establishment of the body axis, cell migration, synaptic plasticity, and a vast range of other biological processes. Protein localization occurs through three mechanisms: protein transport, mRNA localization, and local translation. However, the relative contribution of each process to neuronal polarity remains unknown. Using neurons differentiated from mouse embryonic stem cells, we analyze protein and RNA expression and translation rates in isolated cell bodies and neurites genome-wide. We quantify 7323 proteins and the entire transcriptome, and identify hundreds of neurite-localized proteins and locally translated mRNAs. Our results demonstrate that mRNA localization is the primary mechanism for protein localization in neurites that may account for half of the neurite-localized proteome. Moreover, we identify multiple neurite-targeted non-coding RNAs and RNA-binding proteins with potential regulatory roles. These results provide further insight into the mechanisms underlying the establishment of neuronal polarity.Subcellular localization of RNAs and proteins is important for polarized cells such as neurons. Here the authors differentiate mouse embryonic stem cells into neurons, and analyze the local transcriptome, proteome, and translated transcriptome in their cell bodies and neurites, providing a unique resource for future studies on neuronal polarity.
Genes & Development · 204 Zitationen · DOI
The core promoter is the ultimate target of the vast network of regulatory factors that contribute to the initiation of transcription by RNA polymerase II. Here we describe the MTE (motif ten element), a new core promoter element that appears to be conserved from Drosophila to humans. The MTE promotes transcription by RNA polymerase II when it is located precisely at positions +18 to +27 relative to A(+1) in the initiator (Inr) element. MTE sequences from +18 to +22 relative to A(+1) are important for basal transcription, and a region from +18 to +27 is sufficient to confer MTE activity to heterologous core promoters. The MTE requires the Inr, but functions independently of the TATA-box and DPE. Notably, the loss of transcriptional activity upon mutation of a TATA-box or DPE can be compensated by the addition of an MTE. In addition, the MTE exhibits strong synergism with the TATA-box as well as the DPE. These findings indicate that the MTE is a novel downstream core promoter element that is important for transcription by RNA polymerase II.
Genome Research · 204 Zitationen · DOI
Computational methods for automated genome annotation are critical to our community's ability to make full use of the large volume of genomic sequence being generated and released. To explore the accuracy of these automated feature prediction tools in the genomes of higher organisms, we evaluated their performance on a large, well-characterized sequence contig from the Adh region of Drosophila melanogaster. This experiment, known as the Genome Annotation Assessment Project (GASP), was launched in May 1999. Twelve groups, applying state-of-the-art tools, contributed predictions for features including gene structure, protein homologies, promoter sites, and repeat elements. We evaluated these predictions using two standards, one based on previously unreleased high-quality full-length cDNA sequences and a second based on the set of annotations generated as part of an in-depth study of the region by a group of Drosophila experts. Although these standard sets only approximate the unknown distribution of features in this region, we believe that when taken in context the results of an evaluation based on them are meaningful. The results were presented as a tutorial at the conference on Intelligent Systems in Molecular Biology (ISMB-99) in August 1999. Over 95% of the coding nucleotides in the region were correctly identified by the majority of the gene finders, and the correct intron/exon structures were predicted for >40% of the genes. Homology-based annotation techniques recognized and associated functions with almost half of the genes in the region; the remainder were only identified by the ab initio techniques. This experiment also presents the first assessment of promoter prediction techniques for a significant number of genes in a large contiguous region. We discovered that the promoter predictors' high false-positive rates make their predictions difficult to use. Integrating gene finding and cDNA/EST alignments with promoter predictions decreases the number of false-positive classifications but discovers less than one-third of the promoters in the region. We believe that by establishing standards for evaluating genomic annotations and by assessing the performance of existing automated genome annotation tools, this experiment establishes a baseline that contributes to the value of ongoing large-scale annotation projects and should guide further research in genome informatics.
Nature Structural & Molecular Biology · 190 Zitationen · DOI
RNA · 189 Zitationen · DOI
MicroRNAs are approximately 22-nucleotide (nt) RNAs processed from foldback segments of endogenous transcripts. Some are known to play important gene regulatory roles during animal and plant development by pairing to the messages of protein-coding genes to direct the post-transcriptional repression of these messages. Previously, we developed a computational method called MiRscan, which scores features related to the foldbacks, and used this algorithm to identify new miRNA genes in the nematode Caenorhabditis elegans. In the present study, to identify sequences that might be involved in processing or transcriptional regulation of miRNAs, we aligned sequences upstream and downstream of orthologous nematode miRNA foldbacks. These alignments showed a pronounced peak in sequence conservation about 200 bp upstream of the miRNA foldback and revealed a highly significant sequence motif, with consensus CTCCGCCC, that is present upstream of almost all independently transcribed nematode miRNA genes. Scoring the pattern of upstream/downstream conservation, the occurrence of this sequence motif, and orthology of host genes for intronic miRNA candidates, yielded substantial improvements in the accuracy of MiRscan. Nine new C. elegans miRNA gene candidates were validated using a PCR-sequencing protocol. As previously seen for bacterial RNA genes, sequence features outside of the RNA secondary structure can therefore be very useful for the computational identification of eukaryotic noncoding RNA genes. The total number of confidently identified nematode miRNAs now approaches 100. The improved analysis supports our previous assertion that miRNA gene identification is nearing completion in C. elegans with apparently no more than 20 miRNA genes now remaining to be identified.
Trends in Genetics · 187 Zitationen · DOI
Nature Methods · 177 Zitationen · DOI
Kooperationen7
Bestätigte Forscher↔Partner-Paare aus HU-FIS — Gold-Standard-Positive für das Matching.
IGRK 2403/1: Analyse und Umbau des regulatorischen Genoms
university
IGRK 2403/1: Analyse und Umbau des regulatorischen Genoms
university
SFB/TRR 175/1: Von prädikativen zu mechanistischen Modellen der plastidären Genexpression mittels Hochdurchsatz-Sequenzdaten (TP D01)
university
IGRK 2403: Analyse und Umbau des regulatorischen Genoms
other
IGRK 2403: Analyse und Umbau des regulatorischen Genoms
other
IGRK 2403: Analyse und Umbau des regulatorischen Genoms
university
IGRK 2403/1: Analyse und Umbau des regulatorischen Genoms
university
Stammdaten
Identität, Organisation und Kontakt aus HU-FIS.
- Name
- Prof. Dr. Uwe Ohler
- Titel
- Prof. Dr.
- Fakultät
- Lebenswissenschaftliche Fakultät
- Institut
- Institut für Biologie
- Arbeitsgruppe
- Systems Biology of Gene Regulation (S)
- Telefon
- +49 30 9406 1810
- HU-FIS-Profil
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- Zuletzt gescrapt
- 26.4.2026, 01:10:04