Biology subjects

Teyssier, C.

Publications and source records attributed to Teyssier, C..

6 recordsLinked to original sources

bioRxiv2026

XPO1 controls VDR localization and activity in triple-negative breast cancer cells

The association of cytoplasmic localization of VDR in TNBC tumors and disease aggressivity prompted investigation of its regulation by XPO1. In TNBC cell lines, the XPO1 inhibitors selinexor and eltanexor increased nuclear VDR localization. Their effects were particularly strong when combined with vitamin D treatment. Similarly, XPO1 knockdown increased nuclear VDR levels, both alone and in combination with vitamin D. These results identify XPO1 as an important regulator of VDR subcellular distribution. XPO1 inhibition also enhanced vitamin D-dependent VDR transcriptional activity. Indeed, selinexor, eltanexor, and XPO1 silencing increased vitamin D-dependent CYP24A1 reporter activity and the expression of genes such as CYP24A1 or CDH1. RNA sequencing showed that XPO1 modulation markedly reshaped the vitamin D transcriptional response. The affected genes were mainly involved in metabolism, cell-cycle regulation, protein localization, and cellular organization. Functional analyses demonstrated that cytoplasmic VDR promoted TNBC cell proliferation. Conversely, nuclear VDR was required for the antiproliferative effects of vitamin D. Accordingly, XPO1 inhibition or depletion potentiated vitamin D-mediated growth suppression. This finding suggested functional cooperation between XPO1-dependent export and VDR activity. Finally, high VDR expression was associated with poor disease-free or overall survival only in tumors with high XPO1 expression. Overall, XPO1 negatively regulates VDR nuclear localization and vitamin D responsiveness in TNBC. Targeting XPO1 may therefore enhance the therapeutic potential of vitamin D-based strategies in TNBC.

cell biology↗

bioRxiv2025

Near-infrared spectroscopy-based models correctly classify Abies alba seed origin and predict germination properties

Forestry industry requires high-quantity and quality seeds for afforestation and assisted migration programs. Finding reliable non-destructive methods to characterize seeds would significantly enhance efforts to identify climate-adapted populations. This study presents near-infrared (NIR) spectroscopy models to classify seed origin and predict germination characteristics at different temperatures non-destructively. We focus on Abies alba Mill., a key European forest tree with genetic variation along climatic gradients and seeds with shallow physiological dormancy. Seeds from six populations were analyzed using NIR spectroscopy, and germination was tested at 15{degrees}C, 20{degrees}C, and 25{degrees}C after stratification treatments at 4{degrees}C (0 or 3 weeks). Population classification accuracy using Partial Least Squares Discriminant Analysis was 69%, with significant NIR peaks at 1712, 1929, and 2111 nm, linked to moisture content and storage compounds. NIR spectra explained 51% and 65% of the variation in germination probability and timing using Partial Least Squares Regression, with significant peaks at 1712, 1929, 2111, 1632, and 2073 nm. General Linear Mixed-Effects Models showed that a NIR predictor contributed to 39% of the germination probability variance explained by fixed-effects, and the stratification treatment was the most important driver explaining germination time. Our results proved the utility of NIR-based tools to effectively classify bulked seeds and predict germination, opening new perspectives to nursery and forestry sectors and populations adaptation and adjustments to warming climate. This study will facilitate further investigations on the physiological processes that occur during dormancy, a critical process for forest regeneration given the expected impact of shorter and warmer winters on seed behavior.

ecology↗

bioRxiv2024

Epigenetic memory of temperature during somatic embryo maturation in 2-year-old maritime pine trees

Embryogenesis is a brief but potentially critical phase in the tree life cycle for adaptive phenotypic plasticity. Using somatic embryogenesis in maritime pine, we found that temperature during the maturation phase affects embryo development and post-embryonic tree growth for up to three years. We examined whether this somatic stress memory could stem from temperature- and/or development-induced changes in DNA methylation. To do this, we developed a 200 Mb custom sequence capture bisulfite analysis of genes and promoters to identify differentially methylated cytosines (DMCs) between temperature treatments (18, 23, and 28{degrees}C) and developmental stages (immature and cotyledonary embryos, shoot apical meristem of 2-year-old plants) and investigate if these differences can be mitotically transmitted from embryonic to post-embryonic development (epigenetic memory). We revealed a high prevalence of temperature-induced DMCs in genes (8-14%) compared to promoters (less than 1%) in all 3 cytosine contexts. Developmental DMCs showed a comparable pattern but only in the CG context, and with a high trend towards hypo-methylation, particularly in the promoters. A high percentage of DMCs induced by developmental transitions were found memorized in genes (up to 45-50%) and promoters (up to 90%). In contrast, temperature-induced memory was lower and confined to genes after both embryonic (up to 14%) and post-embryonic development (up to 8%). Using stringent criteria, we identified ten genes involved in defense responses and adaptation, embryo development and chromatin regulation that are candidates for the establishment of a persistent epigenetic memory of temperature sensed during embryo maturation in maritime pine. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=131 HEIGHT=200 SRC="FIGDIR/small/600784v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@17a70f1org.highwire.dtl.DTLVardef@18d186borg.highwire.dtl.DTLVardef@3e27f5org.highwire.dtl.DTLVardef@b15348_HPS_FORMAT_FIGEXP M_FIG C_FIG

plant biology↗

bioRxiv2023

RIP140 regulates HES1 oscillatory expression and mitogenic activity in colon cancer cells

BackgroundThe transcription factor RIP140 (Receptor Interacting Protein of 140 kDa) regulates intestinal homeostasis and tumorigenesis through the Wnt signaling. In this study, we have investigated its effect on the Notch/HES1 signaling pathway. MethodsThe impact on HES1 expression and activity was evaluated in colorectal cancer (CRC) cell lines and in transgenic mice, invalidated or not for the Rip140 gene in the intestinal epithelium. A tumor microarray and transcriptomic data sets were used to investigate RIP140 and HES1 expression in relation with patient survival. Statistical comparisons were performed with Mann-Whitney or Kruskal-Wallis or Chi2 tests. ResultsIn CRC cells, RIP140 positively regulated HES1 gene expression at the transcriptional level via an RBPJ/NICD-mediated mechanism. In support of these in vitro data, RIP140 and HES1 expression significantly correlated in mouse intestine and in a cohort of CRC samples, analyzed by immunohistochemistry, thus supporting the positive regulation of HES1 gene expression by RIP140. Interestingly, when the Notch pathway is fully activated, RIP140 exerted a strong inhibition of HES1 gene transcription controlled by the level of HES1 itself. Moreover, RIP140 directly interacts with HES1 and reversed its mitogenic activity in human CRC cells. In line with this observation, HES1 levels were associated with a better patient survival only when tumors expressed high levels of RIP140. ConclusionsOur data identify RIP140 as a key regulator of the Notch/HES1 signaling pathway with a dual effect on HES1 gene expression at the transcriptional level and a strong impact on colon cancer cell proliferation.

cancer biology↗

bioRxiv2022

Evolutionary insights reveal a new role of PADI2 in transcriptional elongation

Peptidyl arginine deiminases (PADIs) catalyze protein citrullination, a post-translational conversion of arginine to citrulline. The most widely expressed member of this family, PADI2, regulates cellular processes that impact several diseases. We hypothesized that we could gain new insights into PADI2 function through a systematic evolutionary and structural analysis. Here, we identify 20 positively selected PADI2 residues, 16 of which are structurally exposed and maintain PADI2 interactions with cognate proteins. Many of these selected residues reside in non-catalytic regions of PADI2. We validate the importance of a prominent loop in the middle domain that encompasses PADI2 L162, a residue under positive selection. This site is essential for interaction with the transcription elongation factor (P-TEFb) and mediates active transcription of the oncogenes c-MYC, and CCNB1, as well as impacting cellular proliferation. These insights could be key to understanding and addressing the role of the PADI2 c-MYC axis in cancer progression. Significance StatementHere we use a systematic evolutionary analysis to identify positively selected residues in the non-catalytic domain of PADI2 and link the positive selection of key residues to a role in transcription. Specifically, a structurally exposed loop in the PADI2 middle domain encompasses the positively selected residue L162 which is linked to transcription and cellular proliferation. This loop contributes to PADI2 interaction with the P-TEFb complex and cellular proliferation. Our results showcase the utility of combining evolutionary and experimental approaches to dissect the evolution of essential functional processes.

evolutionary biology↗

bioRxiv2020

RIP140 inhibits glycolysis-dependent proliferation of cancer cells by regulating transcriptional crosstalk between hypoxia induced factor and p53

Cancer cells with uncontrolled proliferation preferentially depend on glycolysis to grow, even in the presence of oxygen. The transcriptional co-regulator RIP140 represses the activity of transcription factors that drive cell proliferation and metabolism and plays a role in mammary tumorigenesis. Here we use cell proliferation and metabolic assays to demonstrate that RIP140-deficiency causes a glycolysis-dependent increase in breast tumor growth. We further demonstrate that RIP140 reduces the transcription of the glucose transporter GLUT3 gene, by inhibiting the transcriptional activity of hypoxia inducible factor HIF-2 in cooperation with p53. Interestingly, RIP140 expression was significantly associated with good prognosis only for breast cancer patients with tumors expressing low GLUT3, low HIF-2 and high p53, thus confirming the mechanism of RIP140 anti-tumor activity provided by our experimental data. Overall, our work establishes RIP140 as a critical modulator of the p53/HIF cross-talk to inhibit breast cancer cell glycolysis and proliferation.

cancer biology↗