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Personne

Sandra Eloise Offner

Positions

2008- : Laborantine (Laboratoire du Pr D. Trono), Laboratoire de virologie et génétique, EPFL, Suisse.

2004-2008: Laborantine (Laboratoire du Pr A. Trumpp), ISREC, Suisse.

2004: Assistante de recherche (Laboratoire du Pr G. Corradin), Institut de Biochimie, Université de Lausanne, Suisse.

Éducation

1999 - 2004:

Diplôme en Biologie (spécialités : Immunologie, Biochimie et Pharmacologie)

Université de Lausanne, Suisse.

Juin 1999:

Baccalauréat Scientifique, France.

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Domaines de recherche associés (23)

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Publications associées (30)

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BIO-663: Practical - Trono Lab

Introduction to epigenetics

DNA methylation

DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a g

Cellule souche

vignette|Cellules souches embryonnaires de souris en culture. En biologie cellulaire, une cellule souche est une cellule indifférenciée capable, à la fois, de générer des cellules spécialisées par di

Gène

Un gène, du grec ancien (« génération, naissance, origine »), est, en biologie, une séquence discrète et héritable de nucléotides dont l'expression affecte les caractères d'un organisme. L'ensemble

Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis

Alexandre Coudray, Sagane Dind, Julien Léonard Duc, Laurence Gouzi Abrami, Sandra Eloise Offner, Evaristo Jose Planet Letschert, Laia Simo Riudalbas, Didier Trono

The treatment of colorectal cancer (CRC) is an unmet medical need in absence of early diagnosis. Here, upon characterizing cancer-specific transposable element-driven transpochimeric gene transcripts (TcGTs) produced by this tumor in the SYSCOL cohort, we find that expression of the hominid-restricted retrogene POU5F1B through aberrant activation of a primate-specific endogenous retroviral promoter is a strong negative prognostic biomarker. Correlating this observation, we demonstrate that POU5F1B fosters the proliferation and metastatic potential of CRC cells. We further determine that POU5F1B, in spite of its phylogenetic relationship with the POU5F1/OCT4 transcription factor, is a membrane-enriched protein that associates with protein kinases and known targets or interactors as well as with cytoskeleton-related molecules, and induces intracellular signaling events and the release of trans-acting factors involved in cell growth and cell adhesion. As POU5F1B is an apparently non-essential gene only lowly expressed in normal tissues, and as POU5F1B-containing TcGTs are detected in other tumors besides CRC, our data provide interesting leads for the development of cancer therapies.

2022

Chargement

DUX is a non-essential synchronizer of zygotic genome activation

Alberto De Iaco, Delphine Yvette L Grun, Sandra Eloise Offner, Didier Trono, Sonia Verp

Some of the earliest transcripts produced in fertilized human and mouse oocytes code for DUX, a double homeodomain protein that promotes embryonic genome activation (EGA). Deleting Dux by genome editing at the 1- to 2-cell stage in the mouse impairs EGA and blastocyst maturation. Here, we demonstrate that mice carrying homozygous Dux deletions display markedly reduced expression of DUX target genes and defects in both pre- and post-implantation development, with notably a disruption of the pace of the first few cell divisions and significant rates of late embryonic mortality. However, some Dux-/- embryos give raise to viable pups, indicating that DUX is important but not strictly essential for embryogenesis.

2019

Chargement

Hominoid-Specific Transposable Elements and KZFPs Facilitate Human Embryonic Genome Activation and Control Transcription in Naive Human ESCs

Alexandre Coudray, Julien Léonard Duc, Julien Duc, Sandra Eloise Offner, Evaristo Jose Planet Letschert, Julien Paul André Pontis, Didier Trono, Priscilla Turelli

Expansion of transposable elements (TEs) coincides with evolutionary shifts in gene expression. TEs frequently harbor binding sites for transcriptional regulators, thus enabling coordinated genome-wide activation of species- and context-specific gene expression programs, but such regulation must be balanced against their genotoxic potential. Here, we show that Krüppel-associated box (KRAB)-containing zinc finger proteins (KZFPs) control the timely and pleiotropic activation of TE-derived transcriptional cis regulators during early embryogenesis. Evolutionarily recent SVA, HERVK, and HERVH TE subgroups contribute significantly to chromatin opening during human embryonic genome activation and are KLF-stimulated enhancers in naive human embryonic stem cells (hESCs). KZFPs of corresponding evolutionary ages are simultaneously induced and repress the transcriptional activity of these TEs. Finally, the same KZFP-controlled TE-based enhancers later serve as developmental and tissue-specific enhancers. Thus, by controlling the transcriptional impact of TEs during embryogenesis, KZFPs facilitate their genome-wide incorporation into transcriptional networks, thereby contributing to human genome regulation.

2019

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