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Concept

Histone deacetylase inhibitor

Related publications (29)

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

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

The HDAC inhibitor CI-994 acts as a molecular memory aid by facilitating synaptic and intracellular communication after learning

Johannes Gräff, Jose Vicente Sanchez Mut, Giulia Santoni, Allison Marie Burns

Long-term memory formation relies on synaptic plasticity, neuronal activity-dependent gene transcription, and epigenetic modifications. Multiple studies have shown that HDAC inhibitor (HDACi) treatments can enhance individual aspects of these processes and ...

2022

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

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

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

Notch1-driven T-ALL chromatin landscape is regulated by Tcf1 in hematopoietic progenitors

Mateusz Waldemar Antoszewski

Notch1 receptor signaling is essential for T cell fate specification and physiological thymic T lymphocyte development. Its dysregulation and oncogenic activation are detected in almost 80% of pediatric patients suffering from T cell acute lymphoblastic le ...

EPFL2021

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

Sirt6 deletion in bone marrow-derived cells increases atherosclerosis - Central role of macrophage scavenger receptor 1

Johan Auwerx

Aims: Sirtuin 6 (Sirt6) is a NAD(+)-dependent deacetylase that plays a key role in DNA repair, inflammation and lipid regulation. Sirt6-null mice show severe metabolic defects and accelerated aging. Macrophage-foam cell formation via scavenger receptors is ...

2020

The nuclear receptor corepressor NCoR1 regulates hematopoiesis and leukemogenesis in vivo

Johan Auwerx, Lulu Liu, Wei Zhang

Enhanced understanding of normal and malignant hematopoiesis pathways should facilitate the development of effective clinical treatment strategies for hematopoietic malignancies. Nuclear receptor corepressor 1 (NCoR1) has been implicated in transcriptional ...

AMER SOC HEMATOLOGY2019

Nuclear receptor corepressor 1 represses cardiac hypertrophy

Johan Auwerx, Chao Li, Jun Wang, Yan Liu

The function of nuclear receptor corepressor 1 (NCoR1) in cardiomyocytes is unclear, and its physiological and pathological implications are unknown. Here, we found that cardiomyocyte-specific NCoR1 knockout (CMNKO) mice manifested cardiac hypertrophy at b ...

2019

FORMINg a link between PTSD and AD

Johannes Gräff

Epidemiological evidence suggests that people suffering from post-traumatic stress disorder have a higher risk for developing Alzheimer's disease. The underlying mechanisms, however, remained thus far unexplored. In this issue of The EMBO Journal, Agis-Bal ...

Nature Publishing Group2017

Epigenetic approach for angiostatic therapy: promising combinations for cancer treatment

Paul Joseph Dyson, Patrycja Nowak-Sliwinska, Andrea Brett Gasser

Cancer cells are often dependent on epigenetic pathways for their survival. Consequently, drugs that target the epigenome, rather than the underlying DNA sequence, are currently attracting considerable attention. In recent years, the first epigenetic drugs ...

Springer Verlag2017

The chromatin remodeling factor ISW-1 integrates organismal responses against nuclear and mitochondrial stress

Johan Auwerx, Maroun Bou Sleiman

Age-associated changes in chromatin structure have a major impact on organismal longevity. Despite being a central part of the ageing process, the organismal responses to the changes in chromatin organization remain unclear. Here we show that moderate dist ...

Nature Research2017

Rhythmic modulation of transcriptional burst frequency in circadian gene promoters

Damien Lionel Nicolas

Isogenic cells sharing a common environment present a large degree of heterogeneity in gene expression, and stochasticity inherent to transcription substantially participates in this cell-to-cell variability. Notably, a majority of mammalian genes are tran ...

EPFL2017

The effects of mitochondrial- and histone stress on the C. elegans transcriptome

Johan Auwerx, Maroun Bou Sleiman, Pedro Moral Quiros, Olli Juhani Matilainen

The aim of this study was to explore whether mitochondrial- and histone stress cause any common changes in global gene expression. For this experiment, we performed RNA sequencing from control RNAi, cco-1 RNAi (mitochondrial stress) and his-3 RNAi (histone ...

EPFL Infoscience2017

Lysine acetylation stoichiometry and proteomics analyses reveal pathways regulated by sirtuin 1 in human cells

Diego Chiappe

Lysine acetylation is a widespread posttranslational modification affecting many biological pathways. Recent studies indicate that acetylated lysine residues mainly exhibit low acetylation occupancy, but challenges in sample preparation and analysis make i ...

Amer Soc Biochemistry Molecular Biology Inc2017