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A Tale of Two Tumors: Unraveling the Complexities of Epigenetic Dysregulation in Cancer

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Transposable elements mediate genetic effects altering the expression of nearby genes in colorectal cancer

Didier Trono, Evaristo Jose Planet Letschert, Nikolaos Lykoskoufis

Transposable elements (TEs) are prevalent repeats in the human genome, play a significant role in the regulome, and their disruption can contribute to tumorigenesis. However, TE influence on gene expression in cancer remains unclear. Here, we analyze 275 n ...

2024

Single-cell epigenomic reconstruction of developmental trajectories from pluripotency in human neural organoid systems

Cell fate progression of pluripotent progenitors is strictly regulated, resulting in high human cell diversity. Epigenetic modifications also orchestrate cell fate restriction. Unveiling the epigenetic mechanisms underlying human cell diversity has been di ...

Nature Portfolio2024

Decoding Chromatin Ubiquitylation: A Chemical Biology Perspective

Beat Fierz, Pauline Franz

Since Strahl and Allis proposed the "language of covalent histone modifications", a host of experimental studies have shed light on the different facets of chromatin regulation by epigenetic mechanisms. Initially proposed as a concept for controlling gene ...

Academic Press Ltd- Elsevier Science Ltd2024

Inheritance of H3K9 methylation regulates genome architecture in Drosophila early embryos

Constitutive heterochromatin is essential for transcriptional silencing and genome integrity. The establishment of constitutive heterochromatin in early embryos and its role in early fruitfly development are unknown. Lysine 9 trimethylation of histone H3 ( ...

Springernature2024

A chemical biology approach to decipher chromatin ubiquitylation by RNF168

Pauline Franz

DNA damage signaling following DNA double-strand breaks (DSBs) involves numerous regulating proteins, which dynamically recognize ('read') and alter ('write' or 'erase') histone post-translational modifications (PTMs). Among these PTMs, the ubiquitin syste ...

EPFL2024

During gastrulation, Hox genes are activated in a timesequence that follows the order of the genes along their clusters. This property, which is observed in all animals that develop following a progressive rostral-to-caudal morphogenesis, is associated wit ...

Current Biology Ltd2024

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

Pan-cancer atlas of somatic core and linker histone mutations

Sebastian Martin Waszak

Recent genomic data points to a growing role for somatic mutations altering core histone and linker histone-encoding genes in cancer. However, the prevalence and the clinical and biological implications of histone gene mutations in malignant tumors remain ...

2023

Cis-regulatory effect of HPV integration is constrained by host chromatin architecture in cervical cancers

Daniele Tavernari, Giovanni Ciriello

Human papillomavirus (HPV) infections are the primary drivers of cervical cancers, and often HPV DNA gets integrated into the host genome. Although the oncogenic impact of HPV encoded genes is relatively well known, the cis-regulatory effect of integrated ...

Hoboken2023

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