Enhancer regulieren die Transkription ihrer Zielgene und deren Expression. Sie bieten eine Bindestelle für verschiedenste Transkriptionsfaktoren (TF) und RNA Polymerase II (RNAPII) und unterstützen die Gentranskription durch das Zustandekommen von Chromatinkontakten. Zusätzlich transkribiert RNAPII in Enhancer-Regionen kurze, non-polyadenylierte Transkripte, die man Enhancer-RNA (eRNA) nennt. Der Mechanismus der RNAPII-Rekrutierung und –Regulation an Enhancern ist bisher wenig verstanden, insbesondere wie das Vorhandensein von RNAPII-Modifikationen den Chromatinstatus, -faltung sowie die Genaktivierung beeinflusst. In dieser Arbeit wurden verschiedene Ansätze der Enhancer-Bestimmung miteinander verglichen. Während eine klare Bestimmung des besten Ansatzes sich als komplex erwies, konnte gezeigt werden, dass die Bindung von RNAPII an regulatorische Regionen in Zusammenhang mit TF eine universelle Konstante darstellte. Weiterhin wurden der Status der Enhancer-gekoppelten RNAPII-Aktivierung und deren Transkriptionsaktivität untersucht. Als Hauptergebnis ergab sich, dass der RNAPII-Status mit der Enhancer-Aktivität und daraus folgend mit veränderter Transkriptionsaktivität korreliert ist. Weiterhin konnte gezeigt werden, dass das Vorhandensein extragenischer RNAPII ein neues Werkzeug zur Identifikation von regulatorischen Regionen ist. Erfolgreich konnten regulatorische Regionen in embryonalen Stammzellen der Maus sowie während der neuronalen Differenzierung vorhergesagt und mittels Enhancer-Aktivität in-vivo bestätigt werden. Dabei zeigte sich, dass im Laufe der der neuronalen Differenzierung extragenische RNAPII-Bindung spezifische Aktivierungsmuster aufweist: ihr Transkriptionslevel wird durch Kinasen feinmaschig reguliert und es werden verschiedene Formen maturierter RNA erzeugt. Zusammenfassend konnte RNAPII als Werkzeug zur Identifikation und Charakterisierung regulatorischer Regionen in verschiedenen Zelltypen ausgemacht werden. Selbst mit minimalen RNAPII-Datensätzen ist es möglich, gleichzeitig regulatorische Regionen zu identifizieren als auch ihren eigenen Aktivierungsstatus sowie den ihrer kodierender Genpromotoren zu bestimmen. / Enhancers regulate transcription of target genes and gene expression. They act as recruitment sites for multiple transcription factors (TFs) and RNA polymerase II (RNAPII) and favour transcription of target genes through chromatin contacts. RNAPII at enhancer regions transcribes short and mostly non-polyadenylated transcripts, called enhancer RNAs (eRNAs). The mechanisms of RNAPII recruitment and regulation at enhancers remain ill understood, in particular how signalling through RNAPII modifications may influence chromatin states, looping and gene activation. In this study, I compare enhancer lists defined with different approaches and find that their relation is very complex. However, I find that RNAPII binding co-occurs with TF binding at regulatory regions, independently of the identification approach used. I characterize the state of RNAPII activation at enhancers and its transcriptional activity. I find that RNAPII state reflects enhancer activation state and correlates with different transcriptional outputs. In addition, I demonstrate that extragenic RNAPII is a novel tool to identify regulatory regions. I successfully identified putative regulatory regions in mESC and during neuronal differentiation, with enhancer activity in vivo. Extragenic RNAPII regions have specific activation patterns during neuronal differentiation, are finely regulated at the transcriptional level by kinases and transcribe differently mature RNAs. In conclusion, I establish RNAPII as a tool to identify and characterise regulatory regions in a cell type of interest. With minimal RNAPII datasets it is possible to simultaneously identify regulatory regions, infer their state of activation, and the state of activation of coding gene promoters.

No description available.

No description available.

My dissertation, In the Beginning was the Sign, examines the entangled histories of literary modernism and mathematical modernity and revisits their claim to a radical rupture with the past. Informed by Lacanian psychoanalysis, media theory, and deconstruction, I trace how the interplay of literary and mathematical form transformed classical imaginations of the human. Authors like Carl Einstein, Robert Musil or Ernst Cassirer challenge the organic concept of subject formation as Bildung with a new and purely symbolic kind of mathematical abstraction that informs their writing on both thematic and formal levels. In the tradition of Plato’s Meno, they adduce these new forms of mathematical knowledge to find genuinely modern answers to the classical question of the good life. Paradoxically, in striving to portray their own time as a radical novelty that was able to break with its cultural heritage, these authors summon the canon at its most canonical. The mathematician Hilbert, for instance, rewrites the opening of the Gospel of John, translating logos as ‘sign’ rather than ‘word.’ Analyzing literary, philosophical, and mathematical texts in German, English, and French, I show that the questioning of the logical foundations of thought in the so-called foundational crisis in mathematics was re-mediated through a new genealogical exploration of the foundations of European rationality in the texts of classical antiquity.

The objective of this thesis is to present a study of the political impact of Communism on four individuals who at one stage in their lives thought that Communism was the best political system on earth, and who subsequently became disillusioned ot the point where they considered Communism the worst political system on earth. This thesis tries to answer some of the questions arising from such a study. How did these four people become so enamoured of Communism and later so thoroughly disillusioned with it? What is there about Communism which could so strongly attract and later so thoroughly repel intelligent people? Was disaffection due to the weakness of the people involved, or was it due to weaknesses in the Communist system? Where is the truth to be found regarding the essential nature of Communism: in the official reports and propaganda of the Russian government, or in the opinions of the Communist Party members, or in the writings of those who have been in close contact with the system? The problem is to determine the nature of the attraction of Communism and the nature of its repellent aspects as seen by four of those who have strongly felt, in turn, that attraction and that repulsion.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Ce mémoire propose une étude des lieux de tension entre réalité et fiction dans les récits de Marie-Sissi Labrèche et d'Annie Ernaux. Les dispositifs paradoxaux, qui rendent ambiguë l'appartenance générique de ces œuvres, y sont interrogés sous différents angles. Le premier chapitre est l'occasion d'étudier la manière dont les textes exploitent les éléments paratextuels, notamment par la comparaison des différentes éditions des oeuvres. Les propos tenus par les auteures lors d'entrevues y sont également considérés. Dans le deuxième chapitre, les références culturelles et les éléments intertextuels sont envisagés comme des effets de réalité ou comme des lieux d'ambiguïté. Le troisième chapitre montre que les procédés autoréférentiels mettent en évidence le caractère fictionnel de l'oeuvre chez Labrèche, tandis qu'ils participent à l'effet de réalité chez Ernaux. Le dernier chapitre étudie le traitement de la temporalité dans les récits. En somme, l'hybridité générique qui caractérise le récit contemporain est mise en évidence.

This dissertation investigates the materiality of performative sculpture in the Americas during the long 1970s through artists Beverly Buchanan (1940-2015) and Senga Nengudi (1943). United in their disenchantment with second-wave feminism, Buchanan and Nengudi are situated art-historically in the expanded fields of (post)minimalism, conceptualism, and the Black Arts Movement. These artists realize their objects by sourcing non-traditional artmaking materials within what this dissertation conjures as a haptic imaginary—an intervening corrective to both the second-wave feminist and postmodern art imaginaries of the 1970s. Their materials expose the limitations of the visual and offer alternate models of knowing. For Buchanan’s frustulum series (1978-81), poured concrete, and later, tabby concrete, memorializes the textures of architectural sites to honor experiences of labor and displacement. Tabby concrete, a compound binding agent made of sand and lime, is a localized, inexpensive material that was often used by enslaved people in the southern United States, especially in coastal states like Georgia, which provide access to massive deposits of lime-rich oyster shells. Nengudi’s R.S.V.P. series (1977) of pliable pantyhose and sand are anthropomorphic objects originally meant to be activated; they mimic bodily expansion, endurance, and fatigue. Pantyhose, made mostly of nylon, the world’s first fully synthetic fiber, are the product of decades of scientific and economic development, whose intertwined history with World War II offers a springboard to understand the potency of Nengudi’s experiments with the garment. The artists’ materials become sites of investigation into memory, place, body, erotics, and precarity. By offering new epistemological methods of engagement that retaliate against the hegemony of the visual through their twinned interests in ruins for Buchanan, and remains for Nengudi, the artists realize a new womanist politic. Buchanan and Nengudi deploy, respectively, tabby concrete and pantyhose with sand to transmit historical and embodied knowledge. It is precisely through the activated sensorium of touch—imagined and physical—that the past is transmitted and materialized.

Aus der Einleitung (S. 7): „... Sondergerichte bildeten zudem keine Ausnahmeerscheinung, sondern repräsentierten bald schon den Normalzustand der Rechtsprechung unter dem Nationalsozialismus ...”

Condensine sind essentiell für die Faltung von Chromatin und wurden auch mit der Transkriptionsregulation in Verbindung gebracht. Der zugrunde liegende Mechanismus für die Transkriptionsregulation ist jedoch unklar. Condensin DC in C. elegans ist ein gutes Modell zur Erforschung der Transkriptionsregulation durch Condensine, da es spezifisch für die Dosiskompensation der Gene auf dem X Chromosom benutzt wird. Condensin DC bindet an beide X Chromosome in C. elegans Hermaphroditen und reduziert deren Transkription um die Hälfte. In meiner Dissertation habe ich untersucht, welche Rolle ein dynamisches Binden von Condensin DC an Chromatin spielt und wie dies die Transkription während der Embryogenese reguliert. Condensine binden dynamisch an Chromatin, um es zu komprimieren und durch Bildung von Schlaufen die Transkription zu regulieren. Mit Hilfe von „fluorescence recovery after photobleaching“ (FRAP) habe ich in adulten Darmzellen von C. elegans untersucht, welche Faktoren das dynamische Binden von Condensin DC an die X Chromosomen beeinflussen. Meine Daten zeigen, dass sowohl die ATPase-Domäne von Condensin DC, als auch eine nicht-katalytische Aktivität einer Histon-Demethylase die Bindedynamik von Condensin DC beeinflussen und damit Transkription regulieren. Zusätzlich habe ich mit einem Mikroskopieansatz, der auf dem Nachweis von einzelnen RNA Molekülen beruht (smFISH), die Transkription von mehreren Genen untersucht, die durch Condensin DC während der Embryonalentwicklung reguliert werden. Die aus diesen Daten ermittelten Transkriptionskinetiken deuten darauf hin, dass Condensin DC vorrangig die Häufigkeit der Transkriptionsinitiation reguliert. Zusammenfassend liefert meine Forschung neue Einblicke in die Transkriptionsregulation durch Condensine und kann als Basis für detailliertere, mechanistische Studien der Rolle von Condensinen in der Transkriptionsregulation in C. elegans und auch in anderen Organismen dienen. / Condensins are essential for chromosome compaction and have been implicated in transcription regulation. The mechanistic foundation of this regulatory function is poorly understood. A clear paradigm to address this question is the X-specific condensin DC in C. elegans, which specifically binds to and transcriptionally represses X chromosomes in XX hermaphrodites by 2-fold. In my thesis, I studied condensin DC binding dynamics to the X chromosome and how condensin DC affects transcription kinetics in single embryos. The binding of condensins to chromatin has been described in recent microscopy-based studies as dynamic in processes including loop formation, chromatin compaction and transcription regulation. To study the dynamics of condensin DC binding, I established fluorescence recovery after photobleaching (FRAP) in C. elegans adult intestinal cells. With this method, I studied how the ATPase domain and different histone modifiers regulate the dynamic binding of condensin DC. I found that the ATPase domain is critical for binding of the complex and that the noncatalytic activity of a histone demethylase increases the dynamics of condensin DC binding, which is crucial for its role in transcription regulation. To further study the mechanism of condensin DC in transcription regulation, I used an imaging approach based on widefield single-molecule RNA fluorescence in situ hybridization (smFISH). I obtained thousands of smFISH images for a set of condensin DC-regulated genes and extracted mature and nascent RNA counts in 3D, which I used to determine transcription burst characteristics throughout embryonic development. My data show that condensin DC regulates the frequency of transcription initiation to down-regulate X-chromosomal genes. Taken together, my results provide new insight into condensin-mediated transcription regulation, which can be used to inform future studies on the mechanism of condensins in transcription regulation in C. elegans and other organisms.