Biology subjects

Reyes, C.

Publications and source records attributed to Reyes, C..

9 recordsLinked to original sources

bioRxiv2026

Direct effects on gene transcription revealed by global and CRISPR-targeted oxidative DNA damage

Oxidative stress induces rapid expression changes of specific genes. However, whether these changes are due to direct and local DNA oxidation and whether they depend on the repair machinery is still debated. Here, we show by total RNA-Seq that upon oxidative stress, many genes are either rapidly repressed or activated. The early transcriptional response also includes the activation of many read-through RNAs. Importantly, degradation of the endogenous OGG1 DNA glycosylase showed that the early repression of these genes partially depends on OGG1, therefore demonstrating that these genome expression changes are due to the processing of oxidized DNA. We further demonstrate by ChIPseq against total or S5-phosphorylated RNA polymerase II that transcriptional regulation by oxidative stress involves changes in the recruitment of RNA polymerase II to transcription start sites. Finally, through the use of a chemoptogenetic system allowing the targeting of ROS to chosen genomic loci, we were able to reproduce repression of some genes through the local induction of oxidative DNA damage at their promoters, demonstrating that local DNA oxidation directly affects transcription of genes. Altogether, our results show that local oxidative DNA damage leads to alterations in the activity of specific promoters by a mechanism dependent on repair processes.

genomics↗

bioRxiv2026

NITRITE INCREASES MITOFUSIN-1 LEVELS TO INHIBIT VASCULAR SMOOTH MUSCLE CELL PROLIFERATION AND PREVENT INTIMAL HYPERPLASIA

Vascular disease remains a leading cause of morbidity and mortality and is driven by maladaptive vascular remodeling following injury. Stent-induced vascular injury induces vascular smooth muscle cell (VSMC) phenotypic switching from a contractile to a proliferative state, resulting in intimal hyperplasia (IH), restenosis and compromised vessel function. Nitrite, an endogenous oxidation product of nitric oxide and a dietary constituent, attenuates IH after vascular injury; however, its underlying mechanisms remain incompletely understood. Nitrite is known to modulate mitochondrial structure and function, and dysregulated mitochondrial dynamics have independently been implicated in VSMC proliferation. We therefore hypothesized that nitrite attenuates IH by modulating mitochondrial dynamics to suppress VSMC proliferation. Using rat aortic smooth muscle cells (RASMCs), we demonstrate that nitrite treatment inhibits cell cycle progression and cell proliferation through upregulation of mitofusin-1 (Mfn1), a GTPase that catalyzes mitochondrial fusion. Mechanistically, nitrite increased Mfn1 protein levels by inhibiting Mfn1 proteasomal degradation. Mfn1 deletion resulted in enhanced proliferation, loss of contractile gene expression, and decreased expression of antioxidant enzymes including catalase and glutathione peroxidase. Restoration of cellular antioxidant capacity significantly attenuated proliferation and preserved contractile gene expression in Mfn1-deficient cells. Smooth muscle cell-specific Mfn1 knockout mice subjected to carotid artery ligation injury exhibited exacerbated IH compared to wildtype mice. Nitrite administration significantly decreased IH in wildtype mice but not Mfn1-deficient mice. These findings identify endogenous Mfn1 as a critical regulator of VSMC cell cycle progression and as an essential mediator of the vasoprotective effects of nitrite.

cell biology↗

bioRxiv2026

Fungal hydrophobins unleashed from food waste: production, rodlet assembly, and functional properties in Ganoderma adspersum

Ganoderma adspersum is a white-rot fungus (WRF) that produces amphipathic, surface-active proteins, known as hydrophobins. To explore sustainable routes for protein production and waste valorization, G. adspersum was cultivated under defined shaking conditions using different carbon and nitrogen sources, including apple skin food waste. From these cultures, we report for the first time the isolation and characterization of a novel class I hydrophobin, designated as Gad1. Atomic force microscopy revealed abundant rodlet-like nanostructures consistent with class I hydrophobin assemblies, and Raman spectroscopy confirmed {beta}-sheet enrichment typical of amyloid-like organization. MALDI-TOF mass spectrometry further identified Gad1 along with additional hydrophobin-like proteins in the foam. Hydrophobin-enriched foam extracts were used to form stable oil-in-water emulsions that could be converted into porous, freezedried composite aerogels. These findings expand the known diversity of hydrophobins in whiterot fungi and demonstrate that food-waste-derived substrates can support hydrophobin production and functional biomaterial formation.

biophysics↗

bioRxiv2023

Functional Trajectories after Zebrafish Spinal Cord Transection

Adult zebrafish are capable of anatomical and functional recovery following severe spinal cord injury. Axon growth, glial bridging and adult neurogenesis are hallmarks of cellular regeneration during spinal cord repair. However, the correlation between these cellular regenerative processes and functional recovery remains to be elucidated. Whereas the majority of established functional regeneration metrics measure swim capacity, we hypothesize that gait quality is more directly related to neurological health. Here, we performed a longitudinal swim tracking study for sixty individual zebrafish spanning eight weeks of spinal cord regeneration. Multiple swim parameters as well as axonal and glial bridging were integrated. We established rostral compensation as a new gait quality metric that highly correlates with functional recovery. Tensor component analysis of longitudinal data supports a correspondence between functional recovery trajectories and neurological outcomes. Moreover, our studies predicted and validated that a subset of functional regeneration parameters measured 1 to 2 weeks post-injury is sufficient to predict the regenerative outcomes of individual animals at 8 weeks post-injury. Our findings established new functional regeneration parameters and generated a comprehensive correlative database between various functional and cellular regeneration outputs.

neuroscience↗

bioRxiv2022

Condensin positioning at telomeres by Taz1 promotes telomere disjunction in anaphase

The localization of condensin along chromosomes is crucial for their accurate segregation in anaphase. Condensin is enriched at telomeres but how and for what purpose had remained elusive. Here we show that fission yeast condensin accumulates at telomere repeats through the balancing acts of Taz1, a core component of the shelterin complex that ensures telomeric functions, and Mit1, a nucleosome-remodeler associated with shelterin. We further show that condensin takes part in sister-telomere separation in anaphase, and that this event can be uncoupled from the prior separation of chromosome arms, implying a telomere-specific separation mechanism. Consistent with a cis-acting process, increasing or decreasing condensin occupancy specifically at telomeres modifies accordingly the efficiency of their separation in anaphase. Genetic evidence suggests that condensin promotes sister-telomere separation by counteracting cohesin. Thus, our results reveal a shelterin-based mechanism that enriches condensin at telomeres to drive in cis their separation during mitosis.

cell biology↗

bioRxiv2022

Multi-omics comparison of malignant and normal uveal melanocytes reveals novel molecular features of uveal melanoma.

Uveal Melanoma (UM) is a rare cancer resulting from transformation of melanocytes residing in the uveal tract. Integrative analysis has identified four molecular and clinical subsets in UM. To improve our molecular understanding of UM we performed extensive multi-omics characterization comparing two aggressive UM patient-derived xenograft models with normal choroidal melanocytes, including DNA optical mapping, specific histone modifications, and DNA topology analysis by Hi-C. Our gene expression and cytogenetic analyses suggest that genomic instability is a hallmark of UM. We also identified a recurrent deletion in the BAP1 promoter resulting in loss of expression and associated with high risk of metastases in UM patients. Hi-C revealed chromatin topology changes associated with up-regulation of PRAME, an independent prognostic biomarker in UM and potential therapeutic target. Our findings illustrate how multi-omics approaches can improve the understanding of tumorigenesis and reveals two novel mechanisms of gene expression dysregulation in UM.

genomics↗

bioRxiv2021

PRMT1 regulates EGFR and Wnt signaling pathways and is a promising target for combinatorial treatment of breast cancer

Identifying new therapeutic strategies for triple-negative breast cancer (TNBC) patients is a priority as these patients are highly prone to relapse after chemotherapy. Here, we found that protein arginine methyltransferase 1 (PRMT1) is highly expressed in all breast cancer subtypes. Its depletion decreases cell survival by inducing DNA damage and apoptosis in various breast cancer cell lines. Transcriptomic analysis and chromatin immunoprecipitation revealed that PRMT1 regulates the epidermal growth factor receptor (EGFR) and the Wnt signaling pathways, reported to be activated in TNBC. The enzymatic activity of PRMT1 is also required to stimulate the canonical Wnt pathway. Recently developed type I PRMT inhibitors decrease breast cancer cell proliferation and show anti-tumor activity in a TNBC xenograft model. These inhibitors display synergistic interactions with some chemotherapies used to treat TNBC patients, as well as the EGFR inhibitor, erlotinib. Therefore, targeting PRMT1 in combination with drugs used in the clinic may improve current treatments for TNBC patients. SignificanceThis study highlights the requirement of PRMT1 for breast cancer cell survival and demonstrates the potential of targeting type I PRMTs in combination with chemotherapies in triple-negative breast cancer.

cancer biology↗

bioRxiv2020

Aurora B and Condensin are dispensable for chromosome arm and telomere separation during meiosis II

In mitosis, while the importance of kinetochore-microtubule attachment has been known for many years, increasing evidence suggests that telomere dysfunctions also perturb chromosome segregation by contributing to the formation of chromatin bridges at anaphase. Recent evidence suggests that Aurora B ensures proper chromosome segregation during mitosis not only by controlling kinetochore-microtubule attachment but also by regulating telomere and chromosome arm separation. However, whether and how Aurora-B governs telomere separation during meiosis has remained unknown. Here, we show that fission yeast Aurora B localizes at telomeres during meiosis I and promotes telomere separation independently of the meiotic cohesin Rec8. In meiosis II, Aurora-B controls kinetochore-microtubule attachment but appears dispensable for telomere and chromosome arm separation. Likewise, condensin activity is nonessential in meiosis II for telomere and chromosome arm separation. Thus, in meiosis, the requirements for Aurora-B are distinct at centromeres and telomeres, illustrating the critical differences in the control of chromosome segregation between mitosis and meiosis II.

cell biology↗

bioRxiv2018

Functional Asymmetries between Central and Peripheral Retinal Ganglion Cells in a Diurnal Rodent

The segregated properties of the visual system processing central or peripheral regions of the visual field have been widely studied in the visual cortex and the LGN, but rarely reported in retina. The retina performs complex computational strategies to extract spatial-temporal features that are in coherence with animal behavior and survival. Even if a big effort has been done to functionally characterize different retinal ganglion cell (RGC) types, a clear account of the particular functionality of central and peripheral cells is still missing. Here, using electrophysiological data obtained with a 256-MEA recording system on female diurnal rodent retinas (Octodon degus), we evidenced that peripheral RGCs have larger receptive fields, more sustained, faster and shorter temporal responses and sensitive to higher temporal frequencies with a broader frequency bandwidth than the center. Additionally, we also compared the asymmetries between ON and OFF cell populations present in each region, reporting that these asymmetries are dependent on the eccentricity. Finally, the presence of the asymmetries here reported emphasizes even more the complexity of computational strategies performed by the retina, which could serve as inspiration for the development of artificial visual systems.

neuroscience↗