Biology subjects

Gil, N.

Publications and source records attributed to Gil, N..

6 recordsLinked to original sources

bioRxiv2025

Microbiota and Small Cell Lung Cancer.A casual bystander or a hidden culprit?

The tumor-associated microbiome is a key player in cancer development, progression, prognosis, and therapeutic response. Notably, distinct microbial signatures have been identified across cancer types. Small cell lung carcinoma (SCLC) accounts for approximately 15% of all lung cancer, yet its microbiome remains unclear. Analyzing the bacteriome composition in tissue from ten SCLC cases and in 10 cases of a heterogenous lung pathology group, we found a distinct microbial signature associated with SCLC with significantly lower diversity and higher dissimilarity, characterized by a higher relative abundance of Firmicutes and Bacteroidota, and a markedly different set of dominant genera (Pseudomonas, Streptococcus and Haemophilus) resulting in an increased Proteobacteria-to-Actinobacteria ratio. Unexpectedly, mycobiome analysis comparing pooled samples of these SCLC cases with ten pooled lung adenocarcinoma (LUAD) cases revealed that the fungal genus Taphrina was uniquely represented in SCLC. Strikingly, mycobiome individual analysis of twenty-one additional SCLC cases compared with 10 LUAD cases showed an increased prevalence of Taphrina sp. in SLCL tissue. Overall, the results suggest that SCLC microbiome is distinct from other lung pathologies and uncovers a novel link between the biotrophic plant pathogenic Taphrina and human cancer.

cancer biology↗

bioRxiv2025

A novel deep learning-based framework reveals a continuum of chromatinsensitivities across transcription factors

The genome-wide binding of many transcription factors (TFs) depends not only on the presence of their recognition motifs, but also on the surrounding chromatin context. This raises the question of how binding specificity is achieved, which is essential for the proper activation of regulatory regions during developmental and differentiation processes. Two competing hypotheses have been proposed: either opening is a hierarchical process, whereby chromatin-insensitive TFs bind initially and make the DNA accessible for other TFs; or multiple chromatin-sensitive TFs bind cooperatively, enabling them to overcome the chromatin barrier. Here, using complementary genomic- and deep-learning-based techniques, we provide a quantitative framework to assess chromatin sensitivity of individual TFs, and hone in on the definitions and implications of such sensitivity. Our findings demonstrate that the degree of chromatin sensitivity is a continuum across TFs, showing that regulatory regions are activated neither by a purely hierarchical nor purely cooperative mechanism, but by a mixture of both mechanisms. The presented framework allows for a locus-specific as well as global, quantitative assessment of chromatin sensitivity and should help in understanding the binding behaviour of individual TFs as well as their potential contribution to gene regulation.

genomics↗

bioRxiv2022

Solanum lycopersicum CLASS-II KNOX genes regulate fruit anatomy via gibberellin-dependent and independent pathways.

The pericarp is the predominant tissue determining the structural characteristics of most fruits. However, the molecular and genetic mechanisms controlling pericarp development remain only partially understood. Previous studies have identified that CLASS-II KNOX genes regulate fruit size, shape, and maturation in Arabidopsis thaliana and Solanum lycopersicum. Here we characterized the roles of the Solanum lycopersicum CLASS-II KNOX (TKN-II) genes in pericarp development via a detailed histological, anatomical, and karyotype analysis of the TKN-II knockdown (35S:amiR-TKN-II) fruits. We identify that 35S:amiR-TKN-II pericarps contain more cells around their equatorial perimeter and fewer cell layers than the control. In addition, the cell sizes but not the ploidy levels of these pericarps were dramatically reduced. Further, we demonstrate that fruit shape and pericarp layer number phenotypes of the 35S:amiR-TKN-II fruits can be overridden by the procera mutant, known to induce a constitutive response to the plant hormone gibberellin. However, neither the procera mutation nor exogenous gibberellin application can fully rescue the reduced pericarp width and cell size phenotype of 35S:amiR-TKN-II pericarps. Our findings establish that TKN-II genes regulate tomato fruit anatomy, acting via gibberellin to control fruit shape but utilizing a gibberellin-independent pathway to control the size of pericarp cells. HighlightTomato CLASS-II KNOX genes regulate fruit and pericarp anatomy via GA-dependent and independent pathways.

plant biology↗

bioRxiv2021

OCT4 activates a Suv39h1-repressive antisense lncRNA to couple histone H3 Lysine 9 methylation to pluripotency

Histone H3 Lysine 9 (H3K9) methylation, a characteristic mark of heterochromatin, is progressively implemented during development to contribute to cell fate restriction as differentiation proceeds. For instance, in pluripotent mouse Embryonic Stem (ES) cells the global levels of H3K9 methylation are rather low and increase only upon differentiation. Conversely, H3K9 methylation represents an epigenetic barrier for reprogramming somatic cells back to pluripotency. How global H3K9 methylation levels are coupled with the acquisition and loss of pluripotency remains largely unknown. Here, we identify SUV39H1, a major H3K9 di- and tri-methylase, as an indirect target of the pluripotency network of Transcription Factors (TFs). We find that pluripotency TFs, principally OCT4, activate the expression of an uncharacterized antisense long non-coding RNA to Suv39h1, which we name Suv39h1as. In turn, Suv39h1as downregulates Suv39h1 transcription in cis via a mechanism involving the modulation of the chromatin status of the locus. The targeted deletion of the Suv39h1as promoter region triggers increased SUV39H1 expression and H3K9me2 and H3K9me3 levels, leading to accelerated and more efficient commitment into differentiation. We report, therefore, a simple genetic circuitry coupling the global levels of H3K9 methylation to pluripotency in mouse ES cells.

molecular biology↗

bioRxiv2019

Functional Annotation of Human Long Non-Coding RNAs via Molecular Phenotyping

Long non-coding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes and yet, their functions remain largely unknown. We systematically knockdown 285 lncRNAs expression in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNA exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest to-date lncRNA knockdown dataset with molecular phenotyping (over 1,000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.

genomics↗

bioRxiv2018

Production of spliced long noncoding RNAs specifies regions with increased enhancer activity

Active enhancers in mammals produce enhancer RNAs (eRNAs), that are bidirectionally transcribed, unspliced, and unstable noncoding RNAs. Enhancer regions are also enriched with long noncoding RNA (lncRNA) genes, which are typically spliced and are longer and substantially more stable than eRNAs. In order to explore the relationship between these two classes of RNAs and the implications of lncRNA transcription on enhancer functionality, we analyzed DNAse hypersensitive sites with evidence of bidirectional transcription, which we termed eRNA producing centers (EPCs). A subset of EPCs, which are found very close to the transcription start site of lncRNA genes, exhibit attributes of both enhancers and promoters, including distinctive DNA motifs and a characteristic landscape of bound proteins. These EPCs are associated with a subset of relatively highly active enhancers. This stronger enhancer activity is driven, at least in part, by the presence of evolutionary conserved, directional splicing signals that promote lncRNA production, pointing at a causal role of lncRNA processing in enhancer activity. Together, our results suggest a model whereby the ability of some enhancers to produce lncRNAs, which is conserved in evolution, enhances their activity in a manner likely mediated through maturation of the associated lncRNA.

genomics↗