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Results for “3D genome mapping”

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25 records · Page 2Linked to original sources
PubMed2026

Simmondsia chinensis (jojoba) cake fermentation: A new, sustainable technology for advanced skin and scalp care ingredients.

OBJECTIVE: Simmondsia chinensis is a well-known commercially popular plant from which jojoba oil is extracted. Jojoba cake is a sustainably produced, intractable by-product of the jojoba seed oil extraction currently used principally as a fertilizer or burned as fuel. Fermentation work conducted with various microorganisms, including Lactobacillus plantarum, Saccharomyces cerevisiae and Streptococcus thermophilus, sustainably grown on aqueous jojoba cake fermented the cake, liberating jojoba-based amino acids, peptides and proteins. The ferments have been examined chemically and via in vitro cell and tissue studies to develop new skin and scalp care targeted ingredients. METHODS: The jojoba cake contained nutrients (proteins, sugars and lipids) that self-sustain aqueous bacterial fermentation. The ferments were examined on 3D tissue models in vitro via human genomic microarrays. A ferment produced by Lactobacillus plantarum was further tested in vitro using ELISA protein assays on skin cell cultures. A 56-day clinical study on 46 individuals examined the influence of 1.0% of the Lactobacillus ferment on collagen expression using Diffuse Reflectance Spectroscopy (DRS). RESULTS: Gene responses were measured on 244+ genes known to have skin functions. It was found that the Lactobacillus ferment showed the greatest upregulation of skin-associated genes, and three highly upregulated proteins were examined more closely in vitro using ELISA protein assays: collagen-1A1, protocadherin-18 and opioid growth factor receptor. Each protein was upregulated in a dose-dependent fashion. The collagen analysis by DRS demonstrated a statistically significant increase in collagen fluorescence on Day 28 and Day 56 compared to baseline and placebo cream. Further mapping of the collagen fluorescence was done on the individuals using the active formulation at Days 0, 28 and 56. CONCLUSION: Jojoba cake presents a new source of sustainably grown biomass, but the cake is not suitable for topical applications. Fermentation produces components more suitable for topical care. In vitro studies demonstrated upregulation of three skin proteins associated with healing skin. Further studies also employed a newly emerging spectroscopic technique to measure collagen fluorescence in the skin in vivo, the results supporting in vitro work indicating the ferment made with Lactobacillus was able to stimulate collagen synthesis in the skin.

Lactobacillus↗
PubMed2026

One chromatin, many structures: From ensemble contact maps to single-cell 3D organization.

Understanding how chromatin folds in three dimensions remains challenging because most experimental assays capture low-dimensional projections of an underlying, highly heterogeneous polymer. Here, we present an ensemble-based interpretive framework built on the previously introduced Self-Returning Excluded Volume (SR-EV) model, a minimal generator of chromatin conformations using a nucleosome-indexed coarse-grained representation based on stochastic return rules and excluded-volume geometry. Despite its simplicity, SR-EV recapitulates key experimental signatures across scales: heterogeneous nanoscale packing domains resembling ChromEMT and ChromSTEM observations, sparse and highly variable single-configuration contact patterns analogous to single-cell chromosome conformation capture (Hi-C), and robust ensemble-level contact enrichment consistent with topologically associating domains (TADs). In this framework, Hi-C loop and TAD signatures are interpreted as ensemble-level statistical enrichments rather than invariant features of single-cell conformations. SR-EV is explicitly designed to generate large ensembles of complete three-dimensional chromatin configurations that can be projected consistently onto two-dimensional contact maps and one-dimensional genomic profiles. By introducing architectural-protein effects only through ensemble selection rather than explicit forces, SR-EV supports a separation between intrinsic polymer geometry and regulatory bias and suggests that TAD-like features can emerge as statistical enrichments rather than deterministic three-dimensional structures. Coordination number and probe-based accessibility computed directly from SR-EV provide a unified link between three-dimensional packing, two-dimensional contact maps, and one-dimensional genomic profiles. The main contribution of this work is to show, within a single coarse-grained framework, how these multimodal observables arise as linked projections of the same heterogeneous chromatin ensemble through averaging and conditional sampling. Together, these results establish SR-EV as a minimal and geometrically grounded mesoscale reference framework for interpreting how heterogeneous chromatin ensembles give rise to multimodal experimental observables while remaining consistent with the fact that chromatin organization is realized in individual cells.

Chromatin↗
PubMed2025

A global survey of taxa-metabolic associations across mouse microbiome communities.

Host-microbiota mutualism is rooted in the exchange of dietary and metabolic molecules. Microbial diversity broadens the metabolite pool, with each taxon contributing distinct compounds in varying proportions. In the human microbiome, high variability in consortial composition is largely compensated by similar metabolic functions across different taxa. However, the extent of compensation in lower diversity mouse models, and whether vivaria are metabolically equivalent, is unknown. We provide a searchable resource of microbiome composition variability across 51 murine vivaria and 12 wild mouse colonies worldwide, with vivarium-specific variants mapped according to predicted 3D structures for each microbial species. Our matched metabolomics data show that realized metabolic potential has relatively low variability, providing functional evidence for metabolic compensation. Additionally, variability is related to taxonomic composition rather than vivarium, revealing taxa-metabolite associations that are potentially relevant to phenotypic differences between vivaria. Collectively, this resource offers tools to strengthen microbiome studies and collaborative science.

Animals↗
PubMed2025

An RNA polymerase III tissue and tumor atlas uncovers context-specific activities linked to 3D epigenome regulatory mechanisms.

RNA polymerase III (Pol III) produces a plethora of small noncoding RNA species involved in diverse cellular processes, from transcription regulation and splicing to RNA stability, translation, and proteostasis. Though Pol III activity is broadly coupled with cellular demands for protein synthesis and growth, a more precise understanding of gene-level dynamics and context-specific expression patterns remains missing, in part due to challenges related to sequencing and mapping Pol III-derived small ncRNAs. Here, we establish a predictive multi-tissue map of human Pol III activity across 19 tissues and 23 primary cancer subtypes by comprehensively profiling the chromatin accessibility of canonical Pol III-transcribed gene classes. Our framework relies on the unique relationship between gene accessibility and Pol III transcription, inferring activity through uniform binary classification of ATAC-seq enrichment at Pol III-transcribed genes. By characterizing multi-context gene uniformity, we provide a definition of the core Pol III transcriptome, broadly active across specialized tissues, and catalog genes with varied levels of context specificity. Our genomic Pol III atlas uncovers variable levels of activity across tissues, including sharp contraction of the Pol III transcriptome in heart and brain tissues and frequent expansion across diverse cancers. We show that both tissue- and tumor-specific genes are significantly enriched within lamina-associated domains (LADs), and that aberrant expression of nuclear lamin proteins is sufficient to induce Pol III-emergent patterns at tumor-specific genes. Together, these findings link Pol III dynamics to subnuclear compartmentalization and provide a resource for better understanding Pol III expansion and small RNA biogenesis in cancer.

Journal Article↗
PubMed2026

Nuclear exosome targeting complexes modulate cohesin binding and enhancer-promoter interactions in 3D.

Three-dimensional long-range contacts between enhancers and promoters are thought to be largely determined by loop extrusion driven by the cohesin complex and insulator factors. However, recent evidence also suggests a role for noncoding RNAs, such as enhancer-associated RNAs and promoter upstream transcripts, in shaping enhancer-promoter connectivity. While the nuclear RNA exosome, together with targeting complexes, poly(A) tail exosome targeting connection and nuclear exosome targeting complex, controls the decay of noncoding RNAs, it remains unclear whether these complexes regulate three-dimensional chromatin contacts. Chromatin recruitment maps of the nuclear exosome targeting complex subunit ZCCHC8, the poly(A) tail exosome targeting connection subunit ZFC3H1, and the RNA helicase MTR4 in human cells reveal that these factors associate with sites of enhancer-promoter interactions. Depletion of these factors leads to the accumulation of ncRNAs, notably enhancer-associated RNAs and promoter upstream transcripts, and increases cohesin occupancy at these sites. Chromatin conformation capture analysis reveals that MTR4 modulates long-range enhancer-promoter contacts. Upon loss of MTR4, enhancer-promoter contacts increase while intraloop contacts decrease, suggesting that MTR4 facilitates loop extrusion. These data highlight a key interplay between cohesin-mediated enhancer-promoter interactions and the regulation of noncoding RNAs by nuclear RNA exosome targeting complexes that is consistent with a role for RNA in genome folding.

Cohesins↗
PubMed2026

Foundation model reveals the shared organization of transcription and topologically associating domains.

The three-dimensional organization of chromatin into topologically associating domains (TADs) may impact gene regulation by bringing distant genes into contact. However, studies of TADs' function and their influence on transcription have been constrained by ambiguities in TAD boundary definitions and challenges in directly measuring their regulatory effects. We overcome these limitations by developing species-level consensus TAD maps for human and mouse by using a bag-of-genes approach that exposes an emergent regulatory structure. To quantify TAD-mediated relationships, we use a foundation model trained on 33 million transcriptomes to define a contextual similarity metric that captures higher-order relationships missed by co-expression. We find that TADs are regions of elevated co-regulation, with our framework yielding testable hypotheses about chromatin organization across cellular states. This TAD-linked enhancement is strongest during early development and declines with aging, while cancer cells show distinct TAD usage that shifts with chemotherapy. Together, these findings suggest that chromatin organization acts through probabilistic rather than deterministic mechanisms.

Humans↗
PubMed2026

Integrative modeling of the genome structure and dynamics in fission yeast.

Genome organization in the nucleus is highly structured and dynamic. Recent advances in genomic technology have enabled the measurement of genome-wide architecture and locus-specific motion, yielding contact maps and live-cell trajectories. However, these outcomes are derived from different modalities and are not directly comparable, with their quantitative integration being a key challenge. Here we establish a genome-wide live-cell imaging platform in fission yeast Schizosaccharomyces pombe, tracking 131 chromosomal loci, along with the spindle pole body (SPB) and nucleolus, to construct a quantitative map of locus dynamics. By integrating these dynamics with contact data through polymer modeling of Hi-C data, we build a physics-based "digital twin" of the S. pombe genome consistent with the spatiotemporal dynamics of interphase chromatin. We validate it against genome-wide mobility patterns and known architectural features, including centromere and telomere clustering. The model also identifies distinct dynamical regimes: centromere- and telomere-proximal loci relax within [Formula: see text]150 s, whereas the remaining loci relax within [Formula: see text]70 s. We measure semiperiodic dynamics of SPB motion, including a characteristic peak near 225 s and [Formula: see text] fluctuations. We use the model with SPB-directed forcing to show how these low-frequency components propagate through the genome to drive genome-wide chromatin displacements. Together, this predictive physics-based modeling framework integrates genome structure and dynamics to reveal how nuclear mechanical driving forces shape chromosome motion, linking mechanically driven chromatin responses to genome maintenance and regulation.

Schizosaccharomyces↗