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Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide-Activated Sirtuin 7

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Statistical learning quantifies transposable element-mediated cis-regulation

Didier Trono, Evaristo Jose Planet Letschert, Julien Léonard Duc, Cyril David Son-Tuyên Pulver, Alexandre Coudray, Julien Paul André Pontis, Delphine Yvette L Grun, Shaoline Sheppard, Raphaël Gérard Théodore Michel Marie de Deloÿe et Fourcade de Fondeville

Background: Transposable elements (TEs) have colonized the genomes of most metazoans, and many TE-embedded sequences function as cis-regulatory elements (CREs) for genes involved in a wide range of biological processes from early embryo- genesis to innate ...

2023

Whole genome doubling promotes tumorigenesis through loss of chromatin segregation and compartment repositioning

Ruxandra-Andreea Lambuta

Whole genome doubling (WGD) events are drivers of genetic innovation across vertebrate evolution. While generally detrimental to mammalian organisms, WGDs are crucial in the development of various plants and fungi, as well as for the terminal differentiati ...

EPFL2023

Clinical efficacy of ONC201 in H3K27M-mutant diffuse midline gliomas is driven by disruption of integrated metabolic and epigenetic pathways

Sebastian Martin Waszak, Li Jiang

H3K27M-mutant diffuse midline glioma (DMG) patients have no proven effective therapies. ONC201 has recently demonstrated efficacy in these patients, but the mechanism behind this remains unknown. We assessed clinical outcomes, tumor sequencing, and tissue/ ...

2023

Deciphering the molecular events leading to the global restoration of the chromatin landscape during mitotic exit

Silja Michelle Placzek

Two fundamental properties of embryonic stem cells (ESCs) are their ability to self-renew and differentiate into all somatic cell types. Maintenance of their identity faces major challenges when transitioning through mitosis, as most DNA-binding proteins a ...

EPFL2023

Development of multiplexed single-molecule imaging techniques to study chromatin invasion dynamics of chromatin effector proteins

Kristina Makasheva

DNA-binding proteins physically interact with the DNA and directly affect genomic functions. The eukaryotic genome is compacted into chromatin, limiting the DNA access to nuclear factors. In this Ph.D. thesis, I explored the dynamic mechanisms, that allow ...

EPFL2023

Whole-genome doubling drives oncogenic loss of chromatin segregation

Elisa Oricchio, Daniele Tavernari, Natalya Katanayeva, Ruxandra-Andreea Lambuta, Juan Diaz Miyar, Giovanni Ciriello

Whole-genome doubling (WGD) is a recurrent event in human cancers and it promotes chromosomal instability and acquisition of aneuploidies(1-8). However, the three-dimensional organization of chromatin in WGD cells and its contribution to oncogenic phenotyp ...

NATURE PORTFOLIO2023

Environment-dependent epistasis increases phenotypic diversity in gene regulatory networks

Florence Gauye, Florian Baier

Mutations to gene regulatory networks can be maladaptive or a source of evolutionary novelty. Epistasis con-founds our understanding of how mutations affect the expression patterns of gene regulatory networks, a chal-lenge exacerbated by the dependence of ...

AMER ASSOC ADVANCEMENT SCIENCE2023

Epigenetic plasticity as a signature for memory allocation

Giulia Santoni

Long-lasting memories are stored in a small set of neurons scattered throughout the brain, so-called engram cells. To define a stable engram each region of the brain involved in memory storage recruits between 5 and 20 percent of excitatory neurons. In par ...

EPFL2022

Class I histone deacetylases (HDAC1-3) are histone lysine delactylases

Alexander Lund Nielsen, Carlos Moreno Yruela, Di Zhang

Lysine L-lactylation [K(L-la)] is a newly discovered histone mark stimulated under conditions of high glycolysis, such as the Warburg effect. K(L-la) is associated with functions that are different from the widely studied histone acetylation. While K(L-la) ...

2022

Epigenetic memory aids: Synaptic and molecular effects of HDAC inhibition that support memory formation

Allison Marie Burns

Learning and memory rely on synaptic communication in which intracellular signals are transported to the nucleus to stimulate transcriptional activation. Memory induced transcriptional increases are accompanied by alterations to the epigenetic landscape an ...

EPFL2022

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Development of multiplexed single-molecule imaging techniques to study chromatin invasion dynamics of chromatin effector proteins

Kristina Makasheva

EPFL2023

Whole-genome doubling drives oncogenic loss of chromatin segregation

Elisa Oricchio, Daniele Tavernari, Natalya Katanayeva, Ruxandra-Andreea Lambuta, Juan Diaz Miyar, Giovanni Ciriello

NATURE PORTFOLIO2023

Environment-dependent epistasis increases phenotypic diversity in gene regulatory networks

Florence Gauye, Florian Baier

AMER ASSOC ADVANCEMENT SCIENCE2023

Clinical efficacy of ONC201 in H3K27M-mutant diffuse midline gliomas is driven by disruption of integrated metabolic and epigenetic pathways

Sebastian Martin Waszak, Li Jiang

2023