@misc{BeninaRibeiroGechevetal.2015,
  author    = {Benina, Maria and Ribeiro, Dimas Mendes and Gechev, Tsanko S. and M{\"u}ller-R{\"o}ber, Bernd and Schippers, Jos H. M.},
  title     = {A cell type-specific view on the translation of mRNAs from ROS-responsive genes upon paraquat treatment of Arabidopsis thaliana leaves},
  series = {Plant, cell \& environment : cell physiology, whole-plant physiology, community physiology},
  volume    = {38},
  journal   = {Plant, cell \& environment : cell physiology, whole-plant physiology, community physiology},
  number    = {2},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {0140-7791},
  doi       = {10.1111/pce.12355},
  pages     = {349 -- 363},
  year      = {2015},
  abstract  = {Oxidative stress causes dramatic changes in the expression levels of many genes. The formation of a functional protein through successful mRNA translation is central to a coordinated cellular response. To what extent the response towards reactive oxygen species (ROS) is regulated at the translational level is poorly understood. Here we analysed leaf- and tissue-specific translatomes using a set of transgenic Arabidopsis thaliana lines expressing a FLAG-tagged ribosomal protein to immunopurify polysome-bound mRNAs before and after oxidative stress. We determined transcript levels of 171 ROS-responsive genes upon paraquat treatment, which causes formation of superoxide radicals, at the whole-organ level. Furthermore, the translation of mRNAs was determined for five cell types: mesophyll, bundle sheath, phloem companion, epidermal and guard cells. Mesophyll and bundle sheath cells showed the strongest response to paraquat treatment. Interestingly, several ROS-responsive transcription factors displayed cell type-specific translation patterns, while others were translated in all cell types. In part, cell type-specific translation could be explained by the length of the 5-untranslated region (5-UTR) and the presence of upstream open reading frames (uORFs). Our analysis reveals insights into the translational regulation of ROS-responsive genes, which is important to understanding cell-specific responses and functions during oxidative stress. The study illustrates the response of different Arabidopsis thaliana leaf cells and tissues to oxidative stress at the translational level, an aspect of reactive oxygen species (ROS) biology that has been little studied in the past. Our data reveal insights into how translational regulation of ROS-responsive genes is fine-tuned at the cellular level, a phenomenon contributing to the integrated physiological response of leaves to stresses involving changes in ROS levels.},
  language  = {en}
}
@article{HoffmannHaoShearwinetal.2019,
  author    = {Hoffmann, Stefan A. and Hao, Nan and Shearwin, Keith E. and Arndt, Katja Maren},
  title     = {Characterizing transcriptional interference between converging genes in bacteria},
  series = {ACS synthetic biology},
  volume    = {8},
  journal   = {ACS synthetic biology},
  number    = {3},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {2161-5063},
  doi       = {10.1021/acssynbio.8b00477},
  pages     = {466 -- 473},
  year      = {2019},
  abstract  = {Antisense transcription is common in naturally occurring genomes and is increasingly being used in synthetic genetic circuitry as a tool for gene expression control. Mutual influence on the expression of convergent genes can be mediated by antisense RNA effects and by transcriptional interference (TI). We aimed to quantitatively characterize long-range TI between convergent genes with untranslated intergenic spacers of increasing length. After controlling for antisense RNA-mediated effects, which contributed about half of the observed total expression inhibition, the TI effect was modeled. To achieve model convergence, RNA polymerase processivity and collision resistance were assumed to be modulated by ribosome trailing. The spontaneous transcription termination rate in regions of untranslated DNA was experimentally determined. Our modeling suggests that an elongating RNA polymerase with a trailing ribosome is about 13 times more likely to resume transcription than an opposing RNA polymerase without a trailing ribosome, upon head-on collision of the two.},
  language  = {en}
}
@phdthesis{Mauri2014,
  author    = {Mauri, Marco},
  title     = {A model for sigma factor competition in bacterial cells},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-72098},
  school      = {Universit{\"a}t Potsdam},
  pages     = {167},
  year      = {2014},
  abstract  = {Bacteria respond to changing environmental conditions by switching the global pattern of expressed genes. In response to specific environmental stresses the cell activates several stress-specific molecules such as sigma factors. They reversibly bind the RNA polymerase to form the so-called holoenzyme and direct it towards the appropriate stress response genes. In exponentially growing E. coli cells, the majority of the transcriptional activity is carried out by the housekeeping sigma factor, while stress responses are often under the control of alternative sigma factors. Different sigma factors compete for binding to a limited pool of RNA polymerase (RNAP) core enzymes, providing a mechanism for cross talk between genes or gene classes via the sharing of expression machinery. To quantitatively analyze the contribution of sigma factor competition to global changes in gene expression, we develop a thermodynamic model that describes binding between sigma factors and core RNAP at equilibrium, transcription, non-specific binding to DNA and the modulation of the availability of the molecular components. Association of housekeeping sigma factor to RNAP is generally favored by its abundance and higher binding affinity to the core. In order to promote transcription by alternative sigma subunits, the bacterial cell modulates the transcriptional efficiency in a reversible manner through several strategies such as anti-sigma factors, 6S RNA and generally any kind of transcriptional regulators (e.g. activators or inhibitors). By shifting the outcome of sigma factor competition for the core, these modulators bias the transcriptional program of the cell. The model is validated by comparison with in vitro competition experiments, with which excellent agreement is found. We observe that transcription is affected via the modulation of the concentrations of the different types of holoenzymes, so saturated promoters are only weakly affected by sigma factor competition. However, in case of overlapping promoters or promoters recognized by two types of sigma factors, we find that even saturated promoters are strongly affected. Active transcription effectively lowers the affinity between the sigma factor driving it and the core RNAP, resulting in complex cross talk effects and raising the question of how their in vitro measure is relevant in the cell. We also estimate that sigma factor competition is not strongly affected by non-specific binding of core RNAPs, sigma factors, and holoenzymes to DNA. Finally, we analyze the role of increased core RNAP availability upon the shut-down of ribosomal RNA transcription during stringent response. We find that passive up-regulation of alternative sigma-dependent transcription is not only possible, but also displays hypersensitivity based on the sigma factor competition. Our theoretical analysis thus provides support for a significant role of passive control during that global switch of the gene expression program and gives new insights into RNAP partitioning in the cell.},
  language  = {en}
}
@phdthesis{Nell2009,
  author    = {Nell, Sandra},
  title     = {Vitamin E und der vesikul{\"a}re Transport : Untersuchungen zu den genregulatorischen Funktionen von Vitamin E mittels Microarray- und real time PCR-Analysen in der Maus und funktionellen in vitro Assays in RBL-2H3 Zellen},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-35710},
  school      = {Universit{\"a}t Potsdam},
  year      = {2009},
  abstract  = {Vitamin E wird immer noch als das wichtigste lipophile Antioxidanz in biologischen Membranen betrachtet. In den letzten Jahren hat sich jedoch der Schwerpunkt der Vitamin E-Forschung hin zu den nicht-antioxidativen Funktionen verlagert. Besonderes Interesse gilt dabei dem α-Tocopherol, der h{\"a}ufigsten Vitamin E-Form im Gewebe von S{\"a}ugetieren, und seiner Rolle bei der Regulation der Genexpression. Das Ziel dieser Dissertation war die Untersuchung der genregulatorischen Funktionen von α-Tocoperol und die Identifizierung α-Tocopherol-sensitiver Gene in vivo. Zu diesem Zweck wurden M{\"a}use mit verschiedenen Mengen α-Tocopherol gef{\"u}ttert. Die Analyse der hepatischen Genexpression mit Hilfe von DNA-Microarrays identifizierte 387 α-Tocopherol-sensitive Gene. Funktionelle Clusteranalysen der differentiell exprimierten Gene zeigten einen Einfluss von α-Tocooherol auf zellul{\"a}re Transportprozesse. Besonders solche Gene, die an vesikul{\"a}ren Transportvorg{\"a}ngen beteiligt sind, wurden gr{\"o}ßtenteils durch α-Tocopherol hochreguliert. F{\"u}r Syntaxin 1C, Vesicle-associated membrane protein 1, N-ethylmaleimide-sensitive factor and Syntaxin binding protein 1 konnte eine erh{\"o}hte Expression mittels real time PCR best{\"a}tigt werden. Ein funktioneller Einfluss von α-Tocopherol auf vesikul{\"a}re Transportprozesse konnte mit Hilfe des in vitro β-Hexosaminidase Assays in der sekretorischen Mastzelllinie RBL-2H3 gezeigt werden. Die Inkubation der Zellen mit α-Tocopherol resultierte in einer konzentrationsabh{\"a}ngigen Erh{\"o}hung der PMA/Ionomycin-stimulierten Sekretion der β-Hexosaminidase. Eine erh{\"o}hte Expression ausgew{\"a}hlter Gene, die an der Degranulation beteiligt sind, konnte nicht beobachtet werden. Damit schien ein direkter genregulatorischer Effekt von α-Tocopherol eher unwahrscheinlich. Da eine erh{\"o}hte Sekretion auch mit β-Tocopherol aber nicht mit Trolox, einem hydrophilen Vitamin E-Analogon, gefunden wurde, wurde vermutet, dass α-Tocopherol die Degranulation m{\"o}glicherweise durch seine membranst{\"a}ndige Lokalisation beeinflussen k{\"o}nnte. Die Inkubation der Zellen mit α-Tocopherol resultierte in einer ver{\"a}nderten Verteilung des Gangliosids GM1, einem Lipid raft Marker. Es wird angenommen, dass diese Membranmikrodom{\"a}nen als Plattformen f{\"u}r Signaltransduktionsvorg{\"a}nge fungieren. Ein m{\"o}glicher Einfluss von Vitamin E auf die Rekrutierung/Translokation von Signalproteinen in Membranmikrodom{\"a}nen k{\"o}nnte die beobachteten Effekte erkl{\"a}ren. Eine Rolle von α-Tocopherol im vesikul{\"a}ren Transport k{\"o}nnte nicht nur seine eigene Absorption und seinen Transport beeinflussen, sondern auch eine Erkl{\"a}rung f{\"u}r die bei schwerer Vitamin E-Defizienz auftretenden neuronalen Dysfunktionen bieten. Im zweiten Teil der Arbeit wurde die α-Tocopheroltransferprotein (Ttpa) Knockout-Maus als genetisches Modell f{\"u}r Vitamin E-Defizienz verwendet, um den Effekt von Ttpa auf die Genexpression und die Gewebeverteilung von α-Tocopherol zu analysieren. Ttpa ist ein cytosolisches Protein, das f{\"u}r die selektive Retention von α-Tocopherol in der Leber verantwortlich ist. Die Ttpa-Defizienz resultierte in sehr geringen α-Tocopherol-Konzentrationen im Plasma und den extrahepatischen Geweben. Die Analyse der α-Tocopherol-Gehalte im Gehirn wies auf eine Rolle von Ttpa bei der α-Tocopherol-Aufnahme ins Gehirn hin.},
  language  = {de}
}
@phdthesis{Schoenheit2011,
  author    = {Sch{\"o}nheit, J{\"o}rg},
  title     = {A phagocyte-specific Irf8 gene enhancer establishes early conventional dendritic cell commitment},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-55482},
  school      = {Universit{\"a}t Potsdam},
  year      = {2011},
  abstract  = {Haematopoietic development is a complex process that is strictly hierarchically organized. Here, the phagocyte lineages are a very heterogeneous cell compartment with specialized functions in innate immunity and induction of adaptive immune responses. Their generation from a common precursor must be tightly controlled. Interference within lineage formation programs for example by mutation or change in expression levels of transcription factors (TF) is causative to leukaemia. However, the molecular mechanisms driving specification into distinct phagocytes remain poorly understood. In the present study I identify the transcription factor Interferon Regulatory Factor 8 (IRF8) as the specification factor of dendritic cell (DC) commitment in early phagocyte precursors. Employing an IRF8 reporter mouse, I showed the distinct Irf8 expression in haematopoietic lineage diversification and isolated a novel bone marrow resident progenitor which selectively differentiates into CD8α+ conventional dendritic cells (cDCs) in vivo. This progenitor strictly depends on Irf8 expression to properly establish its transcriptional DC program while suppressing a lineage-inappropriate neutrophile program. Moreover, I demonstrated that Irf8 expression during this cDC commitment-step depends on a newly discovered myeloid-specific cis-enhancer which is controlled by the haematopoietic transcription factors PU.1 and RUNX1. Interference with their binding leads to abrogation of Irf8 expression, subsequently to disturbed cell fate decisions, demonstrating the importance of these factors for proper phagocyte cell development. Collectively, these data delineate a transcriptional program establishing cDC fate choice with IRF8 in its center.},
  language  = {en}
}