Biology subjects

Poot-Hernandez, A. C.

Publications and source records attributed to Poot-Hernandez, A. C..

4 recordsLinked to original sources

bioRxiv2025

Mapping early PRC2 nucleation sites upon Suz12 reintroduction reveals features of de novo Polycomb recruitment

Polycomb domains safeguard cell identity by maintaining lineage-specific chromatin states enriched in repressive histone modifications, preserving the epigenetic memory of cell lineages. While Polycomb Repressive Complex 2 (PRC2) can re-establish its occupancy after perturbation, the mechanisms that guide de novo Polycomb recruitment remain unclear. To address this, we engineered an auxin-inducible degradation system to reversibly deplete and reintroduce the endogenous PRC2 core subunit Suz12 in mouse embryonic stem cells (mESCs). Genome-wide profiling at an early recovery time point revealed [~]1,100 PRC2 nucleation sites, characterized by rapid Suz12 and histone H3K27me3 re-accumulation with strong signal, with minimal impact on gene expression. These sites were significantly enriched at bivalent promoters, coinciding with unmethylated CpG islands and chromatin states associated with developmental regulation, and were largely conserved in differentiated cells. Motif analysis identified G/C-rich DNA sequences associated with E2F and zinc-finger proteins, alongside strong co-occupancy with MTF2 and JARID2, two PRC2 cofactors previously implicated in Polycomb targeting. Notably, a subset of nucleation sites overlapped with long-range chromatin interaction anchors in histone H3K27me3 HiChIP datasets. These findings reveal that PRC2 de novo nucleation sites are associated with a combination of chromatin states, DNA sequence features, cofactor co-occupancy and spatial genome organization, suggesting that epigenetic memory can be re-established through defined genomic and chromatin features. Author summaryPolycomb group proteins are key epigenetic regulators that silence gene expression by establishing and dispersing repressive chromatin domains marked by histone modifications such as histone H3K27me3 and H2AK119ub1 and are critical for defining cell identity. During differentiation, Polycomb domains are dynamically redistributed, implying a mechanism for de novo targeting to specific loci. How the Polycomb Repressive Complex 2 (PRC2) is initially recruited to these nucleation sites and which features stabilize its binding remain poorly understood. To explore this, we studied the characteristics of the de novo recruitment sites of PRC2 in mouse embryonic stem cells (mESCs) using an auxin-inducible degradation (AID) system targeting PRC2 to deplete and reintroduce the core subunit Suz12. We identified recruitment sites after complete clearance of the histone H3K27me3 through ChIP-seq at a very early time point after Suz12 reintroduction. Most nucleation sites were located at bivalent promoters of developmental genes and correlated with unmethylated CpG islands. Motif analysis revealed over-represented sequences and accessory partners such as MTF2 and JARID2, along with long-range chromatin interactions. These nucleation sites were also conserved in differentiated cells, highlighting their potential role in developmental regulation. Our study provides insight into how Polycomb domains are established and how epigenetic memory is maintained in stem cells.

molecular biology↗

bioRxiv2025

Transcriptomic profiling of Debaryomyces hansenii reveals detoxification and stress responses to benzo(a)pyrene exposure

The environmental accumulation of polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene (BaP), poses significant threats to ecosystems and public health due to their persistent nature, mutagenic potential, and well-documented carcinogenicity. In this study, we investigated the ability of the extremophilic yeast Debaryomyces hansenii to activate specialized detoxification mechanisms for BaP degradation, even under nutrient-deprived conditions. When exposed to 100 ppm BaP, D. hansenii eliminated over 70% of the contaminant within three days while maintaining normal growth dynamics. RNA-Seq analysis revealed widespread transcriptional remodeling, with 1179 genes upregulated and 1031 downregulated under BaP-only conditions, and 1067 upregulated and 977 downregulated genes during co-metabolic exposure (2% glucose + 100 ppm BaP), from a total of 6506 annotated genes. Gene Ontology (GO) and KEGG enrichment analyses highlighted the activation of xenobiotic degradation pathways, notably involving cytochrome P450 monooxygenases (CYPs), epoxide hydrolases (EHs), and glutathione S-transferases (GSTs), alongside an enhanced antioxidant response and finely tuned glutathione homeostasis. This work provides the first comprehensive transcriptomic profile of BaP detoxification in D. hansenii, revealing an intricate and highly adaptive stress response. Collectively, these findings position D. hansenii as a promising eukaryotic platform for bioremediation in saline and contaminated environments, especially where conventional microbial candidates fall short due to environmental extremes or nutrient scarcity. ImportancePolycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene (BaP), are long-lasting environmental pollutants with serious health and ecological implications. Although microbial degradation offers a promising strategy for remediation, most efforts have focused on bacterial and filamentous fungal systems, leaving other microbial groups comparatively unexplored. In contrast, extremotolerant yeasts remain largely overlooked despite their inherent resilience. Here, we investigated the marine yeast Debaryomyces hansenii and discovered that it not only tolerates BaP under nutrient-limited conditions but also actively degrades it. This response relies on a combination of detoxifying enzymes and antioxidant defenses, reflecting a well-orchestrated metabolic adaptation to chemical stress. Our findings highlight the untapped and promising potential of D. hansenii as a robust eukaryotic chassis for bioremediation, particularly in environments where conventional microbes may fail to survive.

biochemistry↗

bioRxiv2021

Improved post-stroke spontaneous recovery by astrocytic extracellular vesicles

Spontaneous recovery after a stroke accounts for a major part of the neurological recovery in patients. However limited, the spontaneous recovery is mechanistically driven by axonal restorative processes for which several molecular cues have been previously described. We report the acceleration of spontaneous recovery in a preclinical model of ischemia/reperfusion in rats via a single intracerebroventricular administration of extracellular vesicles released from primary cortical astrocytes. We used MRI, confocal and multiphoton microscopy to correlate the structural remodeling of the corpus callosum and striatocortical circuits with neurological performance over 21 days. We also evaluated the functionality of the corpus callosum by repetitive recordings of compound action potentials to show that the recovery facilitated by astrocytic extracellular vesicles was both anatomical and functional. Our data provide compelling evidence that astrocytes can hasten the basal recovery that naturally occurs post-stroke through the release of cellular mediators contained in extracellular vesicles.

neuroscience↗

bioRxiv2017

A new multi-genomic approach for the study of biogeochemical cycles at global scale: the molecular reconstruction of the sulfur cycle

Despite the great advances in microbial ecology and the explosion of high throughput sequencing, our ability to understand and integrate the global biogeochemical cycles is still limited. Here we propose a novel approach to summarize the complexity of the Sulfur cycle based on the minimum ecosystem concept, the microbial mat model and the relative entropy of protein domains involved in S-metabolism. This methodology produces a single value, called the Sulfur Score (SS), which informs about the specific S-related molecular machinery. After curating an inventory of microorganisms, pathways and genes taking part in this cycle, we benchmark the performance of the SS on a collection of 2,107 non-redundant RefSeq genomes, 900 metagenomes from MG-RAST and 35 metagenomes analyzed for the first time. We find that the SS is able to correctly classify microorganisms known to be involved in the S-cycle, yielding an Area Under the ROC Curve of 0.985. Moreover, when sorting environments the top-scoring metagenomes were hydrothermal vents, microbial mats and deep-sea sediments, among others. This methodology can be generalized to the analysis of other biogeochemical cycles or processes. Provided that an inventory of relevant pathways and microorganisms can be compiled, entropy-based scores could be used to detect environmental patterns and informative samples in multi-genomic scale.

bioinformatics↗