Team Publications UMR3244 - Dynamics of Genetic Information - Institut Curie
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Team Publications
UMR3244 – Dynamics of Genetic Information
Year of publication 2019
Charlotte Lecerf, Maud Kamal, Sophie Vacher, Walid Chemlali, Anne Schnitzler, Claire Morel,
Coraline Dubot, Emmanuelle Jeannot, Didier Meseure, Jerzy Klijanienko, Odette Mariani, Edith
Borcoman, Valentin Calugaru, Nathalie Badois, Anne Chilles, Maria Lesnik, Samar Krhili, Olivier
Choussy, Caroline Hoffmann, Eliane Piaggio, Ivan Bieche, Christophe Le Tourneau (2019 Oct 9)
Immune gene expression in head and neck squamous cell carcinoma patients.
European journal of cancer (Oxford, England : 1990) : 210-223 : DOI : S0959-8049(19)30488-5
Summary
Nivolumab and pembrolizumab targeting programmed cell death protein 1 (PD-1) have
recently been approved among patients with recurrent and/or metastatic head and neck
squamous cell carcinoma (HNSCC) who failed platinum therapy. We aimed to evaluate the
prognostic value of selected immune gene expression in HNSCC.
Mijo Simunovic, Emma Evergren, Andrew Callan-Jones*, Patricia Bassereau* (2019 Oct 7)
Curving Cells Inside and Out: Roles of BAR Domain Proteins in Membrane
Shaping and Its Cellular Implications.
Annual Review of Cell and Developmental Biology : 35 : DOI : 10.1146/annurev-
cellbio-100617-060558
Summary
Many cellular processes rely on precise and timely deformation of the cell membrane. While
many proteins participate in membrane reshaping and scission, usually in highly specialized
ways, Bin/amphiphysin/Rvs (BAR) domain proteins play a pervasive role, as they not only
participate in many aspects of cell trafficking but also are highly versatile membrane
remodelers. Subtle changes in the shape and size of the BAR domain can greatly impact the
way in which BAR domain proteins interact with the membrane. Furthermore, the activity of
BAR domain proteins can be tuned by external physical parameters, and so they behave
differently depending on protein surface density, membrane tension, or membrane shape.
These proteins can form 3D structures that mold the membrane and alter its liquid
properties, even promoting scission under various circumstances. As such, BAR domain
proteins have numerous roles within the cell. Endocytosis is among the most highly studied
processes in which BAR domain proteins take on important roles. Over the years, a more
complete picture has emerged in which BAR domain proteins are tied to almost all
intracellular compartments; examples include endosomal sorting and tubular networks in the
endoplasmic reticulum and T-tubules. These proteins also have a role in autophagy, and their
activity has been linked with cancer. Here, we briefly review the history of BAR domain
protein discovery, discuss the mechanisms by which BAR domain proteins induce curvature,
and attempt to settle important controversies in the field. Finally, we review BAR domain
proteins in the context of a cell, highlighting their emerging roles in cell signaling and
organelle shaping.
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 1Team Publications
UMR3244 – Dynamics of Genetic Information
Julien Hardy, Dingli Dai, Anissia Ait Saada, Ana Teixeira-Silva, Louise Dupoiron, Fatemeh
Mojallali, Karine Fréon, Francoise Ochsenbein, Brigitte Hartmann, Sarah Lambert (2019 Oct 4)
Histone deposition promotes recombination-dependent replication at arrested
forks.
PLoS genetics : e1008441 : DOI : 10.1371/journal.pgen.1008441
Summary
Replication stress poses a serious threat to genome stability. Recombination-Dependent-
Replication (RDR) promotes DNA synthesis resumption from arrested forks. Despite the
identification of chromatin restoration pathways after DNA repair, crosstalk coupling RDR
and chromatin assembly is largely unexplored. The fission yeast Chromatin Assembly
Factor-1, CAF-1, is known to promote RDR. Here, we addressed the contribution of histone
deposition to RDR. We expressed a mutated histone, H3-H113D, to genetically alter
replication-dependent chromatin assembly by destabilizing (H3-H4)2 tetramer. We
established that DNA synthesis-dependent histone deposition, by CAF-1 and Asf1, promotes
RDR by preventing Rqh1-mediated disassembly of joint-molecules. The recombination factor
Rad52 promotes CAF-1 binding to sites of recombination-dependent DNA synthesis,
indicating that histone deposition occurs downstream Rad52. Histone deposition and Rqh1
activity act synergistically to promote cell resistance to camptothecin, a topoisomerase I
inhibitor that induces replication stress. Moreover, histone deposition favors non
conservative recombination events occurring spontaneously in the absence of Rqh1,
indicating that the stabilization of joint-molecules by histone deposition also occurs
independently of Rqh1 activity. These results indicate that histone deposition plays an active
role in promoting RDR, a benefit counterbalanced by stabilizing at-risk joint-molecules for
genome stability.
Michel Wassef, Eric Pasmant, Raphaël Margueron (2019 Oct 3)
“MPNST Epigenetics”-Letter.
Molecular cancer research : MCR : 2139 : DOI : 10.1158/1541-7786.MCR-19-0680
Summary
Khalil Saleh, Amaury Daste, Nicolas Martin, Elvire Pons-Tostivint, Anne Auperin, Ruth Gabriela
Herrera-Gomez, Neus Baste-Rotllan, Francois Bidault, Joel Guigay, Christophe Le Tourneau, Esma
Saada-Bouzid, Caroline Even (2019 Oct 2)
Response to salvage chemotherapy after progression on immune checkpoint
inhibitors in patients with recurrent and/or metastatic squamous cell carcinoma
of the head and neck.
European journal of cancer (Oxford, England : 1990) : 123-129 : DOI : S0959-8049(19)30486-1
Summary
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 2Team Publications
UMR3244 – Dynamics of Genetic Information
Immune checkpoint inhibitors (ICI) are active in patients with recurrent/metastatic squamous
cell carcinoma of the head and neck (R/M SCCHN). Recent data suggest that exposure to ICI
improves response to salvage chemotherapy (SCT) in advanced non-small-cell lung cancer.
We evaluated response to chemotherapy in patients who had progressed on ICI in patients
with R/M SCCHN.
Anissia Ait-Saada, Olga Khorosjutina, Jiang Chen, Karol Kramarz, Vladimir Maksimov, J Peter
Svensson, Sarah Lambert, Karl Ekwall (2019 Oct 1)
Chromatin remodeler Fft3 plays a dual role at blocked DNA replication forks.
Life science alliance : DOI : e201900433
Summary
Here, we investigate the function of fission yeast Fun30/Smarcad1 family of SNF2 ATPase-
dependent chromatin remodeling enzymes in DNA damage repair. There are three Fun30
homologues in fission yeast, Fft1, Fft2, and Fft3. We find that only Fft3 has a function in DNA
repair and it is needed for single-strand annealing of an induced double-strand break.
Furthermore, we use an inducible replication fork barrier system to show that Fft3 has two
distinct roles at blocked DNA replication forks. First, Fft3 is needed for the resection of
nascent strands, and second, it is required to restart the blocked forks. The latter function is
independent of its ATPase activity.
Dubois R., Imbert A., Samacoïts A., Peter M., Bertrand E., Müller F., Walter T. (2019 Sep 24)
A Deep Learning Approach To Identify MRNA Localization Patterns
IEEE 16th International Symposium on Biomedical Imaging (ISBI 2019)IEEE 16th International
Symposium on Biomedical Imaging (ISBI 2019)
Summary
Attner MA*, Keil W*, Benavidez JM, Greenwald I (2019 Sep 23)
HLH-2/E2A Expression Links Stochastic and Deterministic Elements of a Cell
Fate Decision during C. elegans Gonadogenesis
Current Biology : 29 : 1-7 : DOI : https://doi.org/10.1016/j.cub.2019.07.062
Summary
Franck Court, Elisa Le Boiteux, Anne Fogli, Mélanie Müller-Barthélémy, Catherine Vaurs-Barrière,
Emmanuel Chautard, Bruno Pereira, Julian Biau, Jean-Louis Kemeny, Toufic Khalil, Lucie Karayan-
Tapon, Pierre Verrelle, Philippe Arnaud (2019 Sep 20)
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 3Team Publications
UMR3244 – Dynamics of Genetic Information
Transcriptional alterations in glioma result primarily from DNA methylation-
independent mechanisms.
Genome research : 29 : 1605-1621 : DOI : 10.1101/gr.249219.119
Summary
In cancer cells, aberrant DNA methylation is commonly associated with transcriptional
alterations, including silencing of tumor suppressor genes. However, multiple epigenetic
mechanisms, including polycomb repressive marks, contribute to gene deregulation in
cancer. To dissect the relative contribution of DNA methylation-dependent and -independent
mechanisms to transcriptional alterations at CpG island/promoter-associated genes in
cancer, we studied 70 samples of adult glioma, a widespread type of brain tumor, classified
according to their isocitrate dehydrogenase (IDH1) mutation status. We found that most
transcriptional alterations in tumor samples were DNA methylation-independent. Instead,
altered histone H3 trimethylation at lysine 27 (H3K27me3) was the predominant molecular
defect at deregulated genes. Our results also suggest that the presence of a bivalent
chromatin signature at CpG island promoters in stem cells predisposes not only to
hypermethylation, as widely documented, but more generally to all types of transcriptional
alterations in transformed cells. In addition, the gene expression strength in healthy brain
cells influences the choice between DNA methylation- and H3K27me3-associated silencing in
glioma. Highly expressed genes were more likely to be repressed by H3K27me3 than by DNA
methylation. Our findings support a model in which altered H3K27me3 dynamics, more
specifically defects in the interplay between polycomb protein complexes and the brain-
specific transcriptional machinery, is the main cause of transcriptional alteration in glioma
cells. Our study provides the first comprehensive description of epigenetic changes in glioma
and their relative contribution to transcriptional changes. It may be useful for the design of
drugs targeting cancer-related epigenetic defects.
Erik B. Watkins, Jaroslaw Majewski, Eva Y. Chi, Haifei Gao, Jean-Claude Florent, Ludger Johannes
(2019 Sep 20)
Shiga Toxin Induces Lipid Compression: A Mechanism for Generating Membrane
Curvature
Nano letters : 19 : DOI : 10.1021/acs.nanolett.9b03001
Summary
Biomembranes are hard to compress laterally, and membrane area compressibility has not
been associated with biological processes. Using X-ray surface scattering, we observed that
bacterial Shiga toxin compresses lipid packing in a gel phase monolayer upon binding to its
cellular receptor, the glycolipid Gb3. This toxin-induced reorganization of lipid packing
reached beyond the immediate membrane patch that the protein was bound to, and linkers
separating the Gb3 carbohydrate and ceramide moieties modulated the toxin’s capacity to
compress the membrane. Within a natural membrane, asymmetric compression of the toxin-
bound leaflet could provide a mechanism to initiate narrow membrane bending, as observed
upon toxin entry into cells. Such lipid compression and long-range membrane reorganization
by glycolipid-binding proteins represent novel concepts in membrane biology that have
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 4Team Publications
UMR3244 – Dynamics of Genetic Information
direct implications for the construction of endocytic pits in clathrin-independent endocytosis.
Petar Scepanovic, Flavia Hodel, Stanislas Mondot, Valentin Partula, Allyson Byrd, Christian
Hammer, Cécile Alanio, Jacob Bergstedt, Etienne Patin, Mathilde Touvier, Olivier Lantz, Matthew
L Albert, Darragh Duffy, Lluis Quintana-Murci, Jacques Fellay, (2019 Sep 15)
A comprehensive assessment of demographic, environmental, and host genetic
associations with gut microbiome diversity in healthy individuals.
Microbiome : 130 : DOI : 10.1186/s40168-019-0747-x
Summary
The gut microbiome is an important determinant of human health. Its composition has been
shown to be influenced by multiple environmental factors and likely by host genetic
variation. In the framework of the Milieu Intérieur Consortium, a total of 1000 healthy
individuals of western European ancestry, with a 1:1 sex ratio and evenly stratified across
five decades of life (age 20-69), were recruited. We generated 16S ribosomal RNA profiles
from stool samples for 858 participants. We investigated genetic and non-genetic factors
that contribute to individual differences in fecal microbiome composition.
Héctor Climente-González, Chloé-Agathe Azencott, Samuel Kaski, Makoto Yamada (2019 Sep 13)
Block HSIC Lasso: model-free biomarker detection for ultra-high dimensional
data.
Bioinformatics (Oxford, England) : i427-i435 : DOI : 10.1093/bioinformatics/btz333
Summary
Finding non-linear relationships between biomolecules and a biological outcome is
computationally expensive and statistically challenging. Existing methods have important
drawbacks, including among others lack of parsimony, non-convexity and computational
overhead. Here we propose block HSIC Lasso, a non-linear feature selector that does not
present the previous drawbacks.
Eric Victor van Leen, Florencia di Pietro, Yohanns Bellaïche (2019 Sep 12)
Oriented cell divisions in epithelia: from force generation to force anisotropy by
tension, shape and vertices.
Current opinion in cell biology : 9-16 : DOI : S0955-0674(19)30070-5
Summary
Mitotic spindle orientation has been linked to asymmetric cell divisions, tissue
morphogenesis and homeostasis. The canonical pathway to orient the mitotic spindle is
composed of the cortical recruitment factor NuMA and the molecular motor dynein, which
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 5Team Publications
UMR3244 – Dynamics of Genetic Information
exerts pulling forces on astral microtubules to orient the spindle. Recent work has defined a
novel role for NuMA as a direct contributor to force generation. In addition, the exploration of
geometrical and physical cues combined with the study of classical polarity pathways has led
to deeper insights into the upstream regulation of spindle orientation. Here, we focus on how
cell shape, junctions and mechanical tension act to orient spindle pulling forces in epithelia,
and discuss different roles for spindle orientation in epithelia.
Simon Gemble, Anthony Simon, Carole Pennetier, Marie Dumont, Solène Hervé, Franz Meitinger,
Karen Oegema, Raphaël Rodriguez, Geneviève Almouzni, Daniele Fachinetti, Renata Basto (2019
Sep 10)
Centromere Dysfunction Compromises Mitotic Spindle Pole Integrity.
Current biology : CB : 3072-3080.e5 : DOI : S0960-9822(19)30932-7
Summary
Centromeres and centrosomes are crucial mitotic players. Centromeres are unique
chromosomal sites characterized by the presence of the histone H3-variant centromere
protein A (CENP-A) [1]. CENP-A recruits the majority of centromere components, collectively
named the constitutive centromere associated network (CCAN) [2]. The CCAN is necessary
for kinetochore assembly, a multiprotein complex that attaches spindle microtubules (MTs)
and is required for chromosome segregation [3]. In most animal cells, the dominant site for
MT nucleation in mitosis are the centrosomes, which are composed of two centrioles,
surrounded by a protein-rich matrix of electron-dense pericentriolar material (PCM) [4]. The
PCM is the site of MT nucleation during mitosis [5]. Even if centromeres and centrosomes are
connected via MTs in mitosis, it is not known whether defects in either one of the two
structures have an impact on the function of the other. Here, using high-resolution
microscopy combined with rapid removal of CENP-A in human cells, we found that
perturbation of centromere function impacts mitotic spindle pole integrity. This includes
release of MT minus-ends from the centrosome, leading to PCM dispersion and centriole mis-
positioning at the spindle poles. Mechanistically, we show that these defects result from
abnormal spindle MT dynamics due to defective kinetochore-MT attachments. Importantly,
restoring mitotic spindle pole integrity following centromere inactivation lead to a decrease
in the frequency of chromosome mis-segregation. Overall, our work identifies an unexpected
relationship between centromeres and maintenance of the mitotic pole integrity necessary
to ensure mitotic accuracy and thus to maintain genetic stability.
Moitrier Sarah, Pricoupenko Nastassia, Kerjouan Adèle, Oddou Christiane, Destaing Olivier,
Battistella Aude, Silberzan Pascal, Bonnet Isabelle (2019 Sep 3)
Local light-activation of the Src oncoprotein in an epithelial monolayer
promotes collective extrusion
Communications Physics : 2 : 98 : DOI : 10.1038/s42005-019-0198-5
Summary
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 6Team Publications
UMR3244 – Dynamics of Genetic Information
Transformed isolated cells are usually extruded from normal epithelia and subsequently
eliminated. However, multicellular tumors outcompete healthy cells, highlighting the
importance of collective effects. Here, we investigate this situation in vitro by controlling in
space and time the activity of the Src oncoprotein within a normal Madin–Darby Canine
Kidney (MDCK) epithelial cell monolayer. Using an optogenetics approach with cells
expressing a synthetic light-sensitive version of Src (optoSrc), we reversibly trigger the
oncogenic activity by exposing monolayers to well-defined light patterns. We show that small
populations of activated optoSrc cells embedded in the non-transformed monolayer
collectively extrude as a tridimensional aggregate and remain alive, while the surrounding
normal cells migrate towards the exposed area. This phenomenon requires an interface
between normal and transformed cells and is partially reversible. Traction forces show that
Src- activated cells either actively extrude or are pushed out by the surrounding cells in a
non- autonomous way.
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 7You can also read
