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Concept

Histone acetylation and deacetylation

Publications associées (32)

Revealing chromatin-specific functions of histone deacylases

Beat Fierz, Carlos Moreno Yruela

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 ...

2024

Investigating the intra-molecular and inter-molecular effects of post-translational modifications on intrinsically disordered protein regions and structured protein regions

Zhidian Zhang

Post-translational modifications (PTMs) play a pivotal role in regulating protein structure, interaction, and function. Aberrant PTM patterns are associated with diseases. Moreover, individual PTMs have a complex interaction with each other, known as PTM c ...

EPFL2024

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

Ursula Röthlisberger, Sophia Kathryn Johnson

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 ...

Swiss Chemical Soc2024

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

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

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

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

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

Epigenetic remodelling of enhancers in response to estrogen deprivation and re-stimulation

Ludovica Vanzan

Estrogen hormones are implicated in a majority of breast cancers and estrogen receptor alpha (ER), the main nuclear factor mediating estrogen signaling, orchestrates a complex molecular circuitry that is not yet fully elucidated. Here, we investigated geno ...

OXFORD UNIV PRESS2021

SIRT7 modulates the stability and activity of the renal K-Cl cotransporter KCC4 through deacetylation

Johan Auwerx, Dongryeol Ryu, Lilia Noriega Lopez

SIRT7 is a NAD(+)-dependent deacetylase that controls important aspects of metabolism, cancer, and bone formation. However, the molecular targets and functions of SIRT7 in the kidney are currently unknown. In silico analysis of kidney transcripts of the BX ...

2021

Metabolic Rewiring by Loss of Sirt5 Promotes Kras-Induced Pancreatic Cancer Progression

Johan Auwerx

BACKGROUND & AIMS: SIRT5 plays pleiotropic roles via post-translational modifications, serving as a tumor suppressor, or an oncogene, in different tumors. However, the role SIRT5 plays in the initiation and progression of pancreatic ductal adenocarcinoma ( ...

W B SAUNDERS CO-ELSEVIER INC2021

Investigating Crosstalk Among PTMs Provides Novel Insight Into the Structural Basis Underlying the Differential Effects of Nt17 PTMs on Mutant Httex1 Aggregation

Hilal Lashuel, Matteo Dal Peraro, Luciano Andres Abriata, Anass Chiki, Lucien Fabrice Krapp, Rajasekhar Kolla, Zhidian Zhang, Driss Boudeffa

Post-translational modifications (PTMs) within the first 17 amino acids (Nt17) of the Huntingtin protein (Htt) have been shown to inhibit the aggregation and attenuate the toxicity of mutant Htt proteins in vitro and in various models of Huntington’s disea ...

2021

Pharmacological and genetic perturbation establish SIRT5 as a promising target in breast cancer

Johan Auwerx, Bo Li

SIRT5 is a member of the sirtuin family of NAD(+)-dependent protein lysine deacylases implicated in a variety of physiological processes. SIRT5 removes negatively charged malonyl, succinyl, and glutaryl groups from lysine residues and thereby regulates mul ...

SPRINGERNATURE2021

Tuning SAS-6 architecture with monobodies impairs distinct steps of centriole assembly

Pierre Gönczy, Georg Fantner, Oliver Hantschel, Santiago Harald Andany, Niccolo Banterle, Virginie Hamel, Georgios Hatzopoulos, Tatiana Favez

Centrioles are evolutionarily conserved multi-protein organelles essential for forming cilia and centrosomes. Centriole biogenesis begins with self-assembly of SAS-6 proteins into 9-fold symmetrical ring polymers, which then stack into a cartwheel that sca ...

Nature Research2021

Multiplexed Single-Molecule Experiments Reveal Nucleosome Invasion Dynamics of the Cas9 Genome Editor

Beat Fierz, Louise Catherine Bryan, Kristina Makasheva

Single-molecule measurements provide detailed mechanistic insights into molecular processes, for example in genome regulation where DNA access is controlled by nucleosomes and the chromatin machinery. However, real-time single-molecule observations of nucl ...

AMER CHEMICAL SOC2021

Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci

Elisa Oricchio, Daniele Tavernari, Natalya Katanayeva, Stephanie Jocelyne Sungalee, Ruxandra-Andreea Lambuta

In cancer cells, enhancer hijacking mediated by chromosomal alterations and/or increased deposition of acetylated histone H3 lysine 27 (H3K27ac) can support oncogene expression. However, how the chromatin conformation of enhancer-promoter interactions is a ...

2021

The box C/D snoRNP assembly factor Bcd1 interacts with the histone chaperone Rtt106 and controls its transcription dependent activity

Benjamin Marcel Daniel Rothé

Biogenesis of eukaryotic box C/D small nucleolar ribonucleoproteins initiates co-transcriptionally and requires the action of the assembly machinery including the Hsp90/R2TP complex, the Rsa1p:Hit1p heterodimer and the Bcd1 protein. We present genetic inte ...

Nature Research2021

Cognitive epigenetic priming: leveraging histone acetylation for memory amelioration

Johannes Gräff, Allison Marie Burns

Multiple studies have found that increasing histone acetylation by means of histone deacetylase inhibitor (HDACi) treatment can ameliorate memory and rescue cognitive impairments, but their mode of action is not fully understood. In particular, it is uncle ...

2020

NCoR1 Protects Mice From Dextran Sodium Sulfate Induced Colitis by Guarding Colonic Crypt Cells From Luminal Insult

Johan Auwerx

BACKGROUND & AIMS: Colonic stem cells are essential for producing the mucosal lining, which in turn protects stem cells from insult by luminal factors. Discovery of genetic and biochemical events that control stem cell proliferation and differentiation can ...

2020