Nucleosome acidic patch-targeting binuclear ruthenium compounds induce aberrant chromatin condensation

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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 ( ...

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 ...

Histone deacylases are erasers of Nε-acyl-lysine post-translational modifications and have been targeted for decades for the treatment of cancer, neurodegeneration and other disorders. Due to their relatively promiscuous activity on peptide substrates in v ...

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 ...

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 ...

Base excision repair enzymes (BERs) detect and repair oxidative DNA damage with efficacy despite the small size of the defects and their often only minor structural impact. A charge transfer (CT) model for rapid scanning of DNA stretches has been evoked to ...

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 ...

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 ...

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 ...

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 ...

Centromeres are epigenetically defined via the presence of the histone H3 variant CENP-A. Contacting CENP-A nucleosomes, the constitutive centromere associated network (CCAN) and the kinetochore assemble, connecting the centromere to spindle microtubules d ...

The fruit fly Drosophila melanogaster serves as a powerful model organism for advancing our understanding of biological processes, not just by studying its similarities with other organisms including ourselves but also by investigating its differences to u ...

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 ...

Telomeres are nucleoprotein structures at the ends of linear chromosomes, being essential for the maintenance of genomic integrity. Telomeres have a unique structure which distinguishes chromosome termini from DNA damage sites. Shelterin complexes are the ...

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 ...

This journal club by Elisa Oricchio highlights two studies published in 2012, which used chromatin conformation capture methods to detect the formation of self-interacting chromatin regions, known as topologically associating domains (TADs). ...

Telomeres are the nucleoprotein structures found at the ends of linear chromosomes. They ensure that the termini of chromosomes are not inappropriately recognized as sites of DNA damage, and are therefore crucial for genome stability. In spite of the heter ...

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/ ...

The sirtuins are NAD+-dependent lysine deacylases, comprising seven isoforms (SIRT1-7) in humans, which are involved in the regulation of a plethora of biological processes, including gene expression and metabolism. The sirtuins share a common hydrolytic m ...

Temporal activation of Hox genes in mouse pseudo-embryos in vitro initiates at the anterior part of the cluster and is accompanied by asymmetric loading of cohesin. Posterior CTCF sites then successively act as transient insulators, regulating the timed tr ...

Nucleosome acidic patch-targeting binuclear ruthenium compounds induce aberrant chromatin condensation

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Inheritance of H3K9 methylation regulates genome architecture in Drosophila early embryos

Decoding Chromatin Ubiquitylation: A Chemical Biology Perspective

Revealing chromatin-specific functions of histone deacylases

A chemical biology approach to decipher chromatin ubiquitylation by RNF168

A CTCF-dependent mechanism underlies the Hox timer relation to a segmented body plan

Oxidative Defect Detection Within Free and Packed DNA Systems: A Quantum Mechanical/Molecular Mechanics (QM/ MM) Approach

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

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

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

Whole-genome doubling drives oncogenic loss of chromatin segregation

CENP-A and CENP-B collaborate to create an open centromeric chromatin state

Centromere structure and function: lessons from Drosophila

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

Telomere protection against oxidative stress

Pan-cancer atlas of somatic core and linker histone mutations

Chromatin organization in red triangles

Regulation and impact of TERRA R-loops at human telomeres

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

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

Sequential and directional insulation by conserved CTCF sites underlies the Hox timer in stembryos