Coordinated Effects of Sequence Variation on DNA Binding, Chromatin Structure, and Transcription

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Identifying genetic and dietary modulators of metabolic disorders using systems genetics

Long-term consumption of lipid-rich foods can contribute to common metabolic diseases and systemic low-grade inflammation. However, dietary responses and the development of non-communicable diseases are shaped by genetic factors and gene-by-environment int ...

EPFL2023

Chromatin modules and their implication in genomic organization and gene regulation

Bart Deplancke, Judith Franziska Kribelbauer, 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

Statistical learning quantifies transposable element-mediated cis-regulation

Didier Trono, Julien Léonard Duc, Alexandre Coudray, Cyril David Son-Tuyên Pulver, Shaoline Sheppard, Evaristo Jose Planet Letschert, Raphaël Gérard Théodore Michel Marie de Deloÿe et Fourcade de Fondeville, Julien Paul André Pontis, Delphine Yvette L Grun

Background: Transposable elements (TEs) have colonized the genomes of most metazoans, and many TE-embedded sequences function as cis-regulatory elements (CREs) for genes involved in a wide range of biological processes from early embryo- genesis to innate ...

2023

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

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

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

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

Kristina Makasheva

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 ...

EPFL2023

Environment-dependent epistasis increases phenotypic diversity in gene regulatory networks

Florence Gauye, Florian Baier

Mutations to gene regulatory networks can be maladaptive or a source of evolutionary novelty. Epistasis con-founds our understanding of how mutations affect the expression patterns of gene regulatory networks, a chal-lenge exacerbated by the dependence of ...

AMER ASSOC ADVANCEMENT SCIENCE2023

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

Giovanni Ciriello, 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

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

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

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

Whole-genome doubling drives oncogenic loss of chromatin segregation

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

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

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