{ "types" : { "Bookmark" : { "pluralLabel" : "Bookmarks" }, "Publication" : { "pluralLabel" : "Publications" }, "GoldStandardPublication" : { "pluralLabel" : "GoldStandardPublications" }, "GoldStandardBookmark" : { "pluralLabel" : "GoldStandardBookmarks" }, "Tag" : { "pluralLabel" : "Tags" }, "User" : { "pluralLabel" : "Users" }, "Group" : { "pluralLabel" : "Groups" }, "Sphere" : { "pluralLabel" : "Spheres" } }, "properties" : { "count" : { "valueType" : "number" }, "date" : { "valueType" : "date" }, "changeDate" : { "valueType" : "date" }, "url" : { "valueType" : "url" }, "id" : { "valueType" : "url" }, "tags" : { "valueType" : "item" }, "user" : { "valueType" : "item" } }, "items" : [ { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2a8704533a8dfa10f1d5f42ed6d4aef19/slegewie", "tags" : [ "Animals,","Base","Development,","Drosophila","Embryonic","Expression","Gene","Genetic,","Glucose,","Kinetics,","Messenger,","Proteins,","Proteome,","RNA,","Regulation,","Sequence,","Transcription,","Transcriptome","melanogaster," ], "intraHash" : "a8704533a8dfa10f1d5f42ed6d4aef19", "interHash" : "42325feb1689d483604c5222faf8ebb8", "label" : "Quantifying post-transcriptional regulation in the development of Drosophila melanogaster", "user" : "slegewie", "description" : "", "date" : "2025-03-05 15:52:38", "changeDate" : "2025-03-05 15:52:38", "count" : 1, "pub-type": "article", "journal": "Nature Communications", "year": "2018", "url": "", "author": [ "Kolja Becker","Alina Bluhm","Nuria Casas-Vila","Nadja Dinges","Mario Dejung","Sergi Sayols","Clemens Kreutz","Jean-Yves Roignant","Falk Butter","Stefan Legewie" ], "authors": [ {"first" : "Kolja", "last" : "Becker"}, {"first" : "Alina", "last" : "Bluhm"}, {"first" : "Nuria", "last" : "Casas-Vila"}, {"first" : "Nadja", "last" : "Dinges"}, {"first" : "Mario", "last" : "Dejung"}, {"first" : "Sergi", "last" : "Sayols"}, {"first" : "Clemens", "last" : "Kreutz"}, {"first" : "Jean-Yves", "last" : "Roignant"}, {"first" : "Falk", "last" : "Butter"}, {"first" : "Stefan", "last" : "Legewie"} ], "volume": "9","number": "1","pages": "4970","abstract": "Even though proteins are produced from mRNA, the correlation between mRNA levels and protein abundances is moderate in most studies, occasionally attributed to complex post-transcriptional regulation. To address this, we generate a paired transcriptome/proteome time course dataset with 14 time points during Drosophila embryogenesis. Despite a limited mRNA-protein correlation (ρ\u2009=\u20090.54), mathematical models describing protein translation and degradation explain 84\\% of protein time-courses based on the measured mRNA dynamics without assuming complex post transcriptional regulation, and allow for classification of most proteins into four distinct regulatory scenarios. By performing an in-depth characterization of the putatively post-transcriptionally regulated genes, we postulate that the RNA-binding protein Hrb98DE is involved in post-transcriptional control of sugar metabolism in early embryogenesis and partially validate this hypothesis using Hrb98DE knockdown. In summary, we present a systems biology framework for the identification of post-transcriptional gene regulation from large-scale, time-resolved transcriptome and proteome data.", "language" : "eng", "pmid" : "30478415", "file" : "Volltext:C\\:\\\\Users\\\\SL\\\\Zotero\\\\storage\\\\U4MU6BPV\\\\Becker et al. - 2018 - Quantifying post-transcriptional regulation in the development of Drosophila melanogaster.pdf:application/pdf", "issn" : "2041-1723", "pmcid" : "PMC6255845", "doi" : "10.1038/s41467-018-07455-9", "bibtexKey": "becker_quantifying_2018" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2b89a812f2c1f0b5111043a1248a6b362/slegewie", "tags" : [ "Animals,","Cells,","Epithelial","Epithelial-Mesenchymal","Expression","Factor","Factors,","Female,","Gene","Growth","Humans,","Proteins,","Regulation,","Signal","Smad","Transcription","Transduction,","Transforming","Transition,","beta" ], "intraHash" : "b89a812f2c1f0b5111043a1248a6b362", "interHash" : "62ea17a3fd7da77c244db6b3573dcc17", "label" : "Transcriptional regulators ensuring specific gene expression and decision-making at high TGFβ doses", "user" : "slegewie", "description" : "", "date" : "2025-03-05 15:52:38", "changeDate" : "2025-03-05 15:52:38", "count" : 1, "pub-type": "article", "journal": "Life Science Alliance", "year": "2025", "url": "", "author": [ "Laura Hartmann","Panajot Kristofori","Congxin Li","Kolja Becker","Lorenz Hexemer","Stefan Bohn","Sonja Lenhardt","Sylvia Weiss","Björn Voss","Alexander Loewer","Stefan Legewie" ], "authors": [ {"first" : "Laura", "last" : "Hartmann"}, {"first" : "Panajot", "last" : "Kristofori"}, {"first" : "Congxin", "last" : "Li"}, {"first" : "Kolja", "last" : "Becker"}, {"first" : "Lorenz", "last" : "Hexemer"}, {"first" : "Stefan", "last" : "Bohn"}, {"first" : "Sonja", "last" : "Lenhardt"}, {"first" : "Sylvia", "last" : "Weiss"}, {"first" : "Björn", "last" : "Voss"}, {"first" : "Alexander", "last" : "Loewer"}, {"first" : "Stefan", "last" : "Legewie"} ], "volume": "8","number": "1","pages": "e202402859","abstract": "TGFβ-signaling regulates cancer progression by controlling cell division, migration, and death. These outcomes are mediated by gene expression changes, but the mechanisms of decision-making toward specific fates remain unclear. Here, we combine SMAD transcription factor imaging, genome-wide RNA sequencing, and morphological assays to quantitatively link signaling, gene expression, and fate decisions in mammary epithelial cells. Fitting genome-wide kinetic models to our time-resolved data, we find that most of the TGFβ target genes can be explained as direct targets of SMAD transcription factors, whereas the remainder show signs of complex regulation, involving delayed regulation and strong amplification at high TGFβ doses. Knockdown experiments followed by global RNA sequencing revealed transcription factors interacting with SMADs in feedforward loops to control delayed and dose-discriminating target genes, thereby reinforcing the specific epithelial-to-mesenchymal transition at high TGFβ doses. We identified early repressors, preventing premature activation, and a late activator, boosting gene expression responses for a sufficiently strong TGFβ stimulus. Taken together, we present a global view of TGFβ-dependent gene regulation and describe specificity mechanisms reinforcing cellular decision-making.", "language" : "eng", "pmid" : "39542693", "issn" : "2575-1077", "pmcid" : "PMC11565188", "doi" : "10.26508/lsa.202402859", "bibtexKey": "hartmann_transcriptional_2025" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/221bcd3a764eeae1aaeff08c1f56216bc/slegewie", "tags" : [ "Analysis,","Cells,","Estrogens,","Expression","Gene","Genetic","Genetic,","Humans,","MCF-7","Models,","Neoplasm","Processes,","Profiling,","Promoter","Proteins,","Regions,","Single-Cell","Stochastic","Transcription,","bursting,","estrogen","heterogeneity,","modeling,","signaling,","stochastic","transcription," ], "intraHash" : "21bcd3a764eeae1aaeff08c1f56216bc", "interHash" : "ee3519776bb351d1b8b9033f64799c99", "label" : "Estrogen-dependent control and cell-to-cell variability of transcriptional bursting", "user" : "slegewie", "description" : "", "date" : "2025-03-05 15:52:38", "changeDate" : "2025-03-05 15:52:38", "count" : 1, "pub-type": "article", "journal": "Molecular Systems Biology", "year": "2018", "url": "", "author": [ "Christoph Fritzsch","Stephan Baumgärtner","Monika Kuban","Daria Steinshorn","George Reid","Stefan Legewie" ], "authors": [ {"first" : "Christoph", "last" : "Fritzsch"}, {"first" : "Stephan", "last" : "Baumgärtner"}, {"first" : "Monika", "last" : "Kuban"}, {"first" : "Daria", "last" : "Steinshorn"}, {"first" : "George", "last" : "Reid"}, {"first" : "Stefan", "last" : "Legewie"} ], "volume": "14","number": "2","pages": "e7678","abstract": "Cellular decision-making and environmental adaptation are dependent upon a heterogeneous response of gene expression to external cues. Heterogeneity arises in transcription from random switching between transcriptionally active and inactive states, resulting in bursts of RNA synthesis. Furthermore, the cellular state influences the competency of transcription, thereby globally affecting gene expression in a cell-specific manner. We determined how external stimuli interplay with cellular state to modulate the kinetics of bursting. To this end, single-cell dynamics of nascent transcripts were monitored at the endogenous estrogen-responsive GREB1 locus. Stochastic modeling of gene expression implicated a two-state promoter model in which the estrogen stimulus modulates the frequency of transcriptional bursting. The cellular state affects transcriptional dynamics by altering initiation and elongation kinetics and acts globally, as GREB1 alleles in the same cell correlate in their transcriptional output. Our results suggest that cellular state strongly affects the first step of the central dogma of gene expression, to promote heterogeneity in the transcriptional output of isogenic cells.", "language" : "eng", "pmid" : "29476006", "issn" : "1744-4292", "pmcid" : "PMC5825209", "doi" : "10.15252/msb.20177678", "bibtexKey": "fritzsch_estrogen-dependent_2018" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2ececc5edfb975851e24e89f723cab58c/bastian", "tags" : [ "Acetolactate","Acid,","Bacterial","Butyrates","Corynebacterium","Deletion,","Enzyme","Expression","Gene","Inhibitors,","Isoleucine,","Kinetics,","Leucine,","Lysine,","Profiling,","Proteins,","Pyruvic","Sequence","Synthase,","Valine,","glutamicum,","myown" ], "intraHash" : "ececc5edfb975851e24e89f723cab58c", "interHash" : "9cd149b8364b60f0642067f88c464b45", "label" : "Acetohydroxyacid synthase, a novel target for improvement of L-lysine production by Corynebacterium glutamicum", "user" : "bastian", "description" : "", "date" : "2018-02-09 13:18:17", "changeDate" : "2018-02-09 12:18:56", "count" : 1, "pub-type": "article", "journal": "Appl. Environ. Microbiol.", "year": "2009", "url": "", "author": [ "Bastian Blombach","Stephan Hans","Brigitte Bathe","Bernhard J. Eikmanns" ], "authors": [ {"first" : "Bastian", "last" : "Blombach"}, {"first" : "Stephan", "last" : "Hans"}, {"first" : "Brigitte", "last" : "Bathe"}, {"first" : "Bernhard J.", "last" : "Eikmanns"} ], "volume": "75","number": "2","pages": "419--427","abstract": "The influence of acetohydroxy acid synthase (AHAS) on L-lysine production by Corynebacterium glutamicum was investigated. An AHAS with a deleted C-terminal domain in the regulatory subunit IlvN was engineered by truncating the ilvN gene. Compared to the wild-type AHAS, the newly constructed enzyme showed altered kinetic properties, i.e., (i) an about twofold-lower K(m) for the substrate pyruvate and an about fourfold-lower V(max); (ii) a slightly increased K(m) for the substrate alpha-ketobutyrate with an about twofold-lower V(max); and (iii) insensitivity against the inhibitors L-valine, L-isoleucine, and L-leucine (10 mM each). Introduction of the modified AHAS into the L-lysine producers C. glutamicum DM1729 and DM1933 increased L-lysine formation by 43\\% (30 mM versus 21 mM) and 36\\% (51 mM versus 37 mM), respectively, suggesting that decreased AHAS activity is linked to increased L-lysine formation. Complete inactivation of the AHAS in C. glutamicum DM1729 and DM1933 by deletion of the ilvB gene, encoding the catalytic subunit of AHAS, led to L-valine, L-isoleucine, and L-leucine auxotrophy and to further-improved L-lysine production. In batch fermentations, C. glutamicum DM1729 Delta ilvB produced about 85\\% more L-lysine (70 mM versus 38 mM) and showed an 85\\%-higher substrate-specific product yield (0.180 versus 0.098 mol C/mol C) than C. glutamicum DM1729. Comparative transcriptome analysis of C. glutamicum DM1729 and C. glutamicum DM1729 Delta ilvB indicated transcriptional differences for about 50 genes, although not for those encoding enzymes involved in the L-lysine biosynthetic pathway.", "pmid" : "19047397", "issn" : "1098-5336", "pmcid" : "PMC2620725", "language" : "eng", "doi" : "10.1128/AEM.01844-08", "bibtexKey": "blombach_acetohydroxyacid_2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/24eb5c8cfb1d770de7b680bff723465f7/bastian", "tags" : [ "Alanine,","Bacterial","Bacterial,","Biomass,","CO(2)/HCO(3)(−),","Carbon","Corynebacterium","DNA-Binding","Dehydrogenase,","Dioxide,","Diphtheria","Dissolved","DtxR,","Expression","Gene","Glucose,","Glucosephosphate","Proteins,","Regulation,","Thiamin","Thiamine,","Toxin,","Valine,","biosynthesis","carbon","dioxide,","glutamicum,","myown","repressor","toxin" ], "intraHash" : "4eb5c8cfb1d770de7b680bff723465f7", "interHash" : "75535e85947aaa1c453c03c26dfd2dfc", "label" : "Impact of different CO2/HCO3- levels on metabolism and regulation in Corynebacterium glutamicum", "user" : "bastian", "description" : "", "date" : "2018-02-09 13:18:17", "changeDate" : "2018-02-09 12:18:56", "count" : 2, "pub-type": "article", "journal": "J. Biotechnol.", "year": "2013", "url": "", "author": [ "Bastian Blombach","Jens Buchholz","Tobias Busche","Jörn Kalinowski","Ralf Takors" ], "authors": [ {"first" : "Bastian", "last" : "Blombach"}, {"first" : "Jens", "last" : "Buchholz"}, {"first" : "Tobias", "last" : "Busche"}, {"first" : "Jörn", "last" : "Kalinowski"}, {"first" : "Ralf", "last" : "Takors"} ], "volume": "168","number": "4","pages": "331--340","abstract": "We investigated the growth kinetics and transcriptional responses of Corynebacterium glutamicum in environments with low (pCO2\\textless40 mbar) and high (pCO2 ≥ 300 mbar) CO2/HCO3(-) levels compared to standard conditions. When cultivated at high CO2/HCO3(-)-levels, C. glutamicum showed increased (63\\%) biomass to substrate yields during the initial growth phase. Other kinetic parameters such as growth rate (μ), specific glucose consumption rate (qS), and selected enzymatic activities of anaplerotic reactions, the pentose phosphate pathway and the tricarboxylic acid cycle were similar to standard conditions. However, microarray hybridization disclosed a complex transcriptional response involving 117 differentially expressed genes. Among those, 60 genes were assigned to the complete DtxR/RipA regulon controlling iron homeostasis in C. glutamicum. Impaired growth of a ΔdtxR mutant at high CO2/HCO3(-) levels validated the relevance of this master regulator to cope with excessive CO2/HCO3(-) availability. At low CO2/HCO3(-) levels, C. glutamicum grew in a bi-level manner with three distinct growth phases. Differential analyses revealed approximately doubled activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase accompanied by the formation of L-alanine and L-valine during the lowest μ occurring in mid-phase of the cultivation. DNA microarray analysis revealed more than 100 differentially expressed genes in growth phase II compared to phase I including almost all thiamin pyrophosphate (TPP) biosynthesis genes, which were significantly up regulated. Concluding, we hypothesize that C. glutamicum counteracts the lack of CO2/HCO3(-) by triggering TPP biosynthesis for increasing the activities of TPP-dependent enzymes involved in CO2 formation.", "pmid" : "24140290", "issn" : "1873-4863", "language" : "eng", "doi" : "10.1016/j.jbiotec.2013.10.005", "bibtexKey": "blombach_impact_2013" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/20f156189f5ad943ea875c8e9d001792c/bastian", "tags" : [ "Bacterial,","Bicarbonates,","Bioreactors,","Carbon","Catechol","Corynebacterium","Culture","Dioxide,","Expression","Gene","Genetic,","Inhibitors","Lysine,","Media,","O-Methyltransferase","Profiling,","Regulation,","Transcription,","glutamicum,","myown" ], "intraHash" : "0f156189f5ad943ea875c8e9d001792c", "interHash" : "9ac7a3d4aa2c97efbb1a2a7bd96710fc", "label" : "CO\u2082 /HCO\u2083\u207B perturbations of simulated large scale gradients in a scale-down device cause fast transcriptional responses in Corynebacterium glutamicum", "user" : "bastian", "description" : "", "date" : "2018-02-09 13:18:17", "changeDate" : "2018-02-09 12:18:56", "count" : 1, "pub-type": "article", "journal": "Appl. Microbiol. Biotechnol.", "year": "2014", "url": "", "author": [ "Jens Buchholz","Michaela Graf","Andreas Freund","Tobias Busche","Jörn Kalinowski","Bastian Blombach","Ralf Takors" ], "authors": [ {"first" : "Jens", "last" : "Buchholz"}, {"first" : "Michaela", "last" : "Graf"}, {"first" : "Andreas", "last" : "Freund"}, {"first" : "Tobias", "last" : "Busche"}, {"first" : "Jörn", "last" : "Kalinowski"}, {"first" : "Bastian", "last" : "Blombach"}, {"first" : "Ralf", "last" : "Takors"} ], "volume": "98","number": "20","pages": "8563--8572","abstract": "The exploration of scale-down models to imitate the influence of large scale bioreactor inhomogeneities on cellular metabolism is a topic with increasing relevance. While gradients of substrates, pH, or dissolved oxygen are often investigated, oscillating CO2/HCO3 (-) levels, a typical scenario in large industrial bioreactors, is rarely addressed. Hereby, we investigate the metabolic and transcriptional response in Corynebacterium glutamicum wild type as well as the impact on L-lysine production in a model strain exposed to pCO2 gradients of (75-315)\u2009mbar. A three-compartment cascade bioreactor system was developed and characterized that offers high flexibility for installing gradients and residence times to mimic industrial-relevant conditions and provides the potential of accurate carbon balancing. The phenomenological analysis of cascade fermentations imposed to the pCO2 gradients at industry-relevant residence times of about 3.6 min did not significantly impair the process performance, with growth and product formation being similar to control conditions. However, transcriptional analysis disclosed up to 66 differentially expressed genes already after 3.6 min under stimulus exposure, with the overall change in gene expression directly correlateable to the pCO2 gradient intensity and the residence time of the cells.", "pmid" : "25139448", "issn" : "1432-0614", "language" : "eng", "doi" : "10.1007/s00253-014-6014-y", "bibtexKey": "buchholz_co_2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2751d62556f83a4d54902c3b9fac85dfb/bastian", "tags" : [ "(Lipoamide)","Acetates,","Bacterial","Bacterial,","Base","Corynebacterium","Data,","Dehydrogenase","Expression","Gene","Molecular","Proteins,","Pyruvate","Regulation,","Sequence","Sequence,","glutamicum,","myown" ], "intraHash" : "751d62556f83a4d54902c3b9fac85dfb", "interHash" : "9f5f5ec2cc8c58eb2101574f015cd25b", "label" : "RamB is an activator of the pyruvate dehydrogenase complex subunit E1p gene in Corynebacterium glutamicum", "user" : "bastian", "description" : "", "date" : "2018-02-09 13:18:17", "changeDate" : "2018-02-09 12:18:56", "count" : 1, "pub-type": "article", "journal": "J. Mol. Microbiol. Biotechnol.", "year": "2009", "url": "", "author": [ "Bastian Blombach","Annette Cramer","Bernhard J. Eikmanns","Mark Schreiner" ], "authors": [ {"first" : "Bastian", "last" : "Blombach"}, {"first" : "Annette", "last" : "Cramer"}, {"first" : "Bernhard J.", "last" : "Eikmanns"}, {"first" : "Mark", "last" : "Schreiner"} ], "volume": "16","number": "3-4","pages": "236--239","abstract": "In Corynebacterium glutamicum, the transcriptional regulator RamB negatively controls the expression of genes involved in acetate metabolism. Here we show that during growth in media containing glucose and in complex medium without glucose RamB activates expression of the aceE gene, encoding the E1p subunit of the pyruvate dehydrogenase complex. Thus, RamB functions both as repressor and as activator in C. glutamicum.", "pmid" : "17890844", "issn" : "1660-2412", "language" : "eng", "doi" : "10.1159/000108782", "bibtexKey": "blombach_ramb_2009" } ] }