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Decoding Chromatin Ubiquitylation: A Chemical Biology Perspective

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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

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

Daniele Tavernari

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 ...

Wiley2023

Exploring the role of transcriptional and post-transcriptional processes in mRNA co-expression

Benjamin Joao Clément Antonin Hadrien Martin

Co-expression of two or more genes at the single-cell level is usually associated with functional co-regulation. While mRNA co-expression-measured as the correlation in mRNA levels-can be influenced by both transcriptional and post-transcriptional events, ...

Wiley2023

cgNA+: A sequence-dependent coarse-grain model of double-stranded nucleic acids

Rahul Sharma

DNA mechanics plays a crucial role in many biological processes, including nucleosome positioning and protein-DNA interactions. It is believed that nature employs epigenetic modifications in DNA to further regulate gene expression. Moreover, double-strande ...

EPFL2023

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

Denis Duboule, Lucille Delisle, Alexandre Gauthier Aurèle Mayran, Hocine Rekaik, Célia Corinne Renée Bochaton

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 ...

NATURE PORTFOLIO2023

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

SARS-CoV-2 hijacks a cell damage response, which induces transcription of a more efficient Spike S-acyltransferase

Didier Trono, Françoise Gisou van der Goot Grunberg, Laurence Gouzi Abrami, Béatrice Kunz, Francisco De Magalhães Sarmento Ribeiro De Mesquita, Lucie Josepha Marie Bracq, Audrey Geneviève Chuat, Nattawadee Panyain

SARS-CoV-2 infection requires Spike protein-mediated fusion between the viral and cellular membranes. The fusogenic activity of Spike depends on its post-translational lipid modification by host S-acyltransferases, predominantly ZDHHC20. Previous observati ...

Nature Research2023

The THO complex counteracts TERRA R-loop-mediated telomere fragility in telomerase(+) cells and telomeric recombination in ALT(+) cells

Joachim Lingner, Rita Valador Fernandes

Telomeres are the nucleoprotein structures at the ends of linear chromosomes. Telomeres are transcribed into long non-coding Telomeric Repeat-Containing RNA (TERRA), whose functions rely on its ability to associate with telomeric chromatin. The conserved T ...

OXFORD UNIV PRESS2023

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

Alexander Lund Nielsen

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 ...

Wiley-VCH Verlag GmbH2023

Telomere protection against oxidative stress

Thu Trang Nguyen

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 ...

EPFL2023

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

Sebastian Martin Waszak

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

Regulation and impact of TERRA R-loops at human telomeres

Rita Valador Fernandes

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 ...

EPFL2023

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

Beat Fierz, Harsh Nagpal, Wei Cai

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 ...

Nature Portfolio2023