TET1 regulates gene expression and repression of endogenous retroviruses independent of DNA demethylation.

DNA methylation (5-methylcytosine (5mC)) is critical for genome stability and transcriptional regulation in mammals. The discovery that ten-eleven translocation (TET) proteins catalyze the oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) revolutionized our perspective on the complexity and regulation of DNA modifications. However, to what extent the regulatory functions of TET1 can be attributed to its catalytic activity remains unclear. Here, we use genome engineering and quantitative multi-omics approaches to dissect the precise catalytic vs. non-catalytic functions of TET1 in murine embryonic stem cells (mESCs). Our study identifies TET1 as an essential interaction hub for multiple chromatin modifying complexes and a global regulator of histone modifications. Strikingly, we find that the majority of transcriptional regulation depends on non-catalytic functions of TET1. In particular, we show that TET1 is critical for the establishment of H3K9me3 and H4K20me3 at endogenous retroviral elements (ERVs) and their silencing that is independent of its canonical role in DNA demethylation. Furthermore, we provide evidence that this repression of ERVs depends on the interaction between TET1 and SIN3A. In summary, we demonstrate that the non-catalytic functions of TET1 are critical for regulation of gene expression and the silencing of endogenous retroviruses in mESCs

Chapter 2 - Philology’s roommate: hermeneutics, antiquity, and the seminar

This chapter starts from the extraordinary historical circumstance that Schleiermacher and Schlegel, a theologian and classical scholar and philosopher, who both had a huge influence on the development of their disciplines and the institution of the university, shared lodgings as students. It explores their relationship, and the importance of it for their subsequent careers, and expands from this to consider how the seminary, as dominant theological educational institution, was overtaken in the university by the seminar – to explore how both educational forums show similar negotiations of the dynamic between personal, affective relationships and methodological rigour. It thus raises questions about how the public and the private, emotion and objectivity became values of scholarship between philology and theology in the universit

Chapter 2 - Philology’s roommate: hermeneutics, antiquity, and the seminar

This chapter starts from the extraordinary historical circumstance that Schleiermacher and Schlegel, a theologian and classical scholar and philosopher, who both had a huge influence on the development of their disciplines and the institution of the university, shared lodgings as students. It explores their relationship, and the importance of it for their subsequent careers, and expands from this to consider how the seminary, as dominant theological educational institution, was overtaken in the university by the seminar – to explore how both educational forums show similar negotiations of the dynamic between personal, affective relationships and methodological rigour. It thus raises questions about how the public and the private, emotion and objectivity became values of scholarship between philology and theology in the universit