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The integrated stress response contributes to tRNA synthetase-associated peripheral neuropathy

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Chromatin modules and their implication in genomic organization and gene regulation

Judith Franziska Kribelbauer, Bart Deplancke, Guido Van Mierlo

Regulation of gene expression is a complex but highly guided process. While genomic technologies and computational approaches have allowed high-throughput mapping of cis-regulatory elements (CREs) and their interactions in 3D, their precise role in regulat ...

ELSEVIER SCIENCE LONDON2023

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

Astrocyte-targeting RNA interference against mutated superoxide dismutase 1 induces motoneuron plasticity and protects fast-fatigable motor units in a mouse model of amyotrophic lateral sclerosis

Patrick Aebischer, Bernard Schneider, Cylia Cloé Rochat, Nathalie Marie Géraldine Bernard

In amyotrophic lateral sclerosis (ALS) caused by SOD1 gene mutations, both cell-autonomous and noncell-autonomous mechanisms lead to the selective degeneration of motoneurons (MN). Here, we evaluate the therapeutic potential of gene therapy targeting mutat ...

WILEY2022

Context-dependent enhancer function revealed by targeted inter-TAD relocation

Denis Duboule, Lucille Delisle, Guillaume Andrey, Christopher Chase Bolt

Here the authors show that a strong enhancer sequence can be controlled by the chromatin environment provided by a topologically associated domain (TAD) located nearby. An enhancer relocated by homologous recombination takes all the hallmarks of its new ne ...

Nature Portfolio2022

The role of the NF-kappaB pathway in Amyotrophic lateral sclerosis pathogenesis

Emma Charlotta Källstig

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative motor disorder, which results in death within a few years of diagnosis. While the cause of most cases of ALS is unknown, 10% of cases are familial (fALS), and associated with mutations in one of ov ...

EPFL2023

Central and peripheral delivered AAV9-SMN are both efficient but target different pathomechanisms in a mouse model of spinal muscular atrophy

Bernard Schneider

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by loss of the SMN1 gene and low SMN protein levels. Although lower motor neurons are a primary target, there is evidence that peripheral organ defects contribute to SMA. Current SMA gene ther ...

2022

Whole-genome doubling drives oncogenic loss of chromatin segregation

Juan Diaz Miyar, Elisa Oricchio, Natalya Katanayeva, Daniele Tavernari, Ruxandra-Andreea Lambuta

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 ...

NATURE PORTFOLIO2023

Efficient and sensitive profiling of RNA–protein interactions using TLC-CLIP

Didier Trono, Julien Léonard Duc, Christina Ernst

RNA-binding proteins are instrumental for post-transcriptional gene regulation, controlling all aspects throughout the lifecycle of RNA molecules. However, transcriptome-wide methods to profile RNA-protein interactions in vivo remain technically challengin ...

2023

A satellite DNA array barcodes chromosome 7 and regulates totipotency via ZFP819

Didier Trono, Gabriela Ecco

Mammalian genomes are a battleground for genetic conflict between repetitive elements and KRAB-zinc finger proteins (KZFPs). We asked whether KZFPs can regulate cell fate by using ZFP819, which targets a satellite DNA array, ZP3AR. ZP3AR coats megabase reg ...

2022

Tcf1 is essential for initiation of oncogenic Notch1-driven chromatin topology in T-ALL

Christelle Dubey, Freddy Radtke, Ute Koch, Nadine Fournier, Mateusz Waldemar Antoszewski, Marianne Nkosi, Tara Kimberly Sugrue

NOTCH1 is a well-established lineage specifier for T cells and among the most frequently mutated genes throughout all subclasses of T cell acute lymphoblastic leukemia (T-ALL). How oncogenic NOTCH1 signaling launches a leukemia-prone chromatin landscape du ...

AMER SOC HEMATOLOGY2022

Sulfur-cycling chemolithoautotrophic microbial community dominates a cold, anoxic, hypersaline Arctic spring

Ianina Altshuler

Background Gypsum Hill Spring, located in Nunavut in the Canadian High Arctic, is a rare example of a cold saline spring arising through thick permafrost. It perennially discharges cold (similar to 7 degrees C), hypersaline (7-8% salinity), anoxic (similar ...

BMC2023

Integrative transcriptome analyses of Transposable Elements (TEs) and genes contribute to a better understanding of colorectal cancer

Eunji Shin

Cancer is the second leading cause of death worldwide. Cancer develops through multiple hallmark functions including apoptosis evasion, unlimited replicative potential, metastasis, and immune avoidance. Over the past few decades, researchers have reported ...

EPFL2022

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

Modeling and analysis of miniaturized magnetorheological valve for fluidic actuation

Sofia Lydia Ntella

Fluidic actuation enables movement in a wide range of mechanical systems, from simple laboratory devices to more complex industrial machinery. Fluids are used to generate motion of mechanical pieces. The term "fluids" encompasses two types of technologies: ...

EPFL2023

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

Comprehensive analysis of the circadian nuclear and cytoplasmic transcriptome in mouse liver

Felix Naef, Cédric Gobet, Benjamin Dieter Weger, Clémence Yumie Syloun Hurni

In eukaryotes, RNA is synthesised in the nucleus, spliced, and exported to the cytoplasm where it is translated and finally degraded. Any of these steps could be subject to temporal regulation during the circadian cycle, resulting in daily fluctuations of ...

PUBLIC LIBRARY SCIENCE2022

GCN2 adapts protein synthesis to scavenging-dependent growth

Hsin-Jung Li

Pancreatic cancer cells with limited access to free amino acids can grow by scavenging extracellular protein. In a murine model of pancreatic cancer, we performed a genome-wide CRISPR screen for genes required for scavenging-dependent growth. The screen id ...

2022

Ribo-DT: An automated pipeline for inferring codon dwell times from ribosome profiling data

Felix Naef, Cédric Gobet

Protein synthesis is an energy consuming process characterised as a pivotal and highly regulated step in gene expression. The net protein output is dictated by a combination of translation initiation, elongation and termination rates that have remained dif ...

ACADEMIC PRESS INC ELSEVIER SCIENCE2022

The role and transcriptional regulation of FAM46A in adipocyte differentiation

Ann-Kristin Hov

Obesity is currently a leading global health concern. Treatments include undergoing a weight-loss regimen. However, successful weight-loss is variable, where the heritability of obesity is considered part of the cause. This patient variability to weight-lo ...

EPFL2021