Sebastian Bultmann

ARID1A mutations protect follicular lymphoma from FAS-dependent immune surveillance by reducing RUNX3/ETS1-driven FAS-expression

Martina Antoniolli, Maria Solovey, Johannes Adrian Hildebrand, Tabea Freyholdt et autres

The cell death receptor FAS and its ligand (FASLG) play crucial roles in the selection of B cells during the germinal center (GC) reaction. Failure to eliminate potentially harmful B cells via FAS can lead to lymphoproliferation and the development of B …

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ARID1A Mutations Protect Follicular Lymphoma from FAS-dependent Immune Surveillance by Reducing RUNX3/ETS1-Driven FAS-Expression

Martina Antoniolli, Maria Solovey, Carolin Dorothea Strobl, Deepak Bararia et autres

ABSTRACT The cell death receptor FAS and its ligand (FASLG) play crucial roles in the selection of B cells during the germinal center (GC) reaction. Failure to eliminate potentially harmful B cells via FAS can lead to lymphoproliferation and the development B …

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Comprehensive chromatin proteomics resolves functional phases of pluripotency and identifies changes in regulatory components

Enes Ugur, Alexandra de la Porte, Weihua Qin, Sebastian Bultmann et autres

The establishment of cellular identity is driven by transcriptional and epigenetic regulators of the chromatin proteome - the chromatome. Comprehensive analyses of the chromatome composition and dynamics can therefore greatly improve our understanding of gene regulatory mechanisms. Here, we developed an accurate …

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Comprehensive chromatin proteomics resolves functional phases of pluripotency

Enes Ugur, Alexandra de la Porte, Sebastian Bultmann, Micha Drukker et autres

Abstract The establishment of cellular identity is driven by transcriptional and epigenetic regulation exerted by the components of the chromatin proteome - the chromatome. However, chromatome composition and its dynamics in functional phases of pluripotency have not been comprehensively analyzed thus limiting …

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

Paul Stolz, Angelo Salazar Mantero, Andrey Tvardovskiy, Enes Ugur et autres

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 …

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Spatial organization of transcribed eukaryotic genes

Susanne Leidescher, Johannes Ribisel, Simon Ullrich, Yana N. Feodorova et autres

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ARID1A Controls a Novel Transcriptional Network Regulating FAS in Follicular Lymphoma

Martina Antoniolli, Maria Solovey, Deepak Bararia, Carolin Dorothea Strobl et autres

Abstract Follicular lymphoma (FL) is a clinically and genetically heterogeneous disease. Somatic gene mutations contribute to the heterogeneous clinical course of FL. ARID1A, which encodes for a subunit of the SWI/SNF chromatin remodeling complex, is among the most commonly mutated genes in …

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Phosphorylation of the HP1β hinge region sequesters KAP1 in heterochromatin and promotes the exit from naïve pluripotency

Weihua Qin, Enes Ugur, Christopher B. Mulholland, Sebastian Bultmann et autres

Heterochromatin binding protein HP1β plays an important role in chromatin organization and cell differentiation, however the underlying mechanisms remain unclear. Here, we generated HP1β-/- embryonic stem cells and observed reduced heterochromatin clustering and impaired differentiation. We found that during stem cell differentiation, …

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A genome-wide knock-out screen for actors of epigenetic silencing reveals new regulators of germline genes and 2-cell like cell state

Nikhil Gupta, Lounis Yakhou, Julien Richard Albert, Fumihito Miura et autres

Abstract Epigenetic mechanisms are essential to establish and safeguard cellular identities in mammals. They dynamically regulate the expression of genes, transposable elements, and higher-order chromatin structures. Expectedly, these chromatin marks are indispensable for mammalian development and alterations often lead to diseases such …

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Epiblast morphogenesis is controlled by selective mRNA decay triggered by LIN28A relocation

Miha Modic, Igor Ruiz de los Mozos, Sebastian Steinhauser, Emiel van Genderen et autres

The embryonic progression from naïve to primed pluripotency is accompanied by the rapid decay of pluripotency-associated mRNAs and a concomitant radical morphogenetic sequence of epiblast polarization, rosette formation and lumenogenesis. The mechanisms triggering and linking these events remain poorly understood. Guided by …

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Loss-of-function mutations in the histone methyltransferase EZH2 promote chemotherapy resistance in AML

Julia Kempf, Sabrina Weser, Michael D. Bartoschek, Klaus Hans Metzeler et autres

Chemotherapy resistance is the main impediment in the treatment of acute myeloid leukaemia (AML). Despite rapid advances, the various mechanisms inducing resistance development remain to be defined in detail. Here we report that loss-of-function mutations (LOF) in the histone methyltransferase EZH2 have …

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Identification of permissive amber suppression sites for efficient non-canonical amino acid incorporation in mammalian cells

Michael D. Bartoschek, Enes Ugur, Tuan‐Anh Nguyen, Geraldine Rodschinka et autres

The genetic code of mammalian cells can be expanded to allow the incorporation of non-canonical amino acids (ncAAs) by suppressing in-frame amber stop codons (UAG) with an orthogonal pyrrolysyl-tRNA synthetase (PylRS)/tRNAPylCUA (PylT) pair. However, the feasibility of this approach is substantially hampered …

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