Background: Nucleosomes consist of DNA wrapped around a histone octamer core like thread on a spool to condense DNA as chromatin into chromosomes. Diseases such as cancer or inflammation lead to cell death, chromatin fragmentation and release of nucleosomes into the blood. The Nu.Q™ platform measures circulating nucleosomes in the blood of humans that result from disease and has been used to detect and identify cancer even at early stages. The objectives of this study are to quantify and better characterize nucleosomes in dogs with various stages of hemangiosarcoma (HSA) using this ELISA-based assay. Samples from 77 dogs with a confirmed diagnosis of hemangiosarcoma and 134 healthy controls were utilized for this study. The HSA samples were recruited from the Texas A&M University Small Animal Clinic (TAMU-SAC) or purchased from biobanks. All control samples were recruited from the TAMU-SAC.
Results: Dogs with hemangiosarcoma had a 6.6-fold increase in their median plasma nucleosome concentrations compared to controls (AUC 92.9 %). Elevated nucleosome concentrations were seen at all stages of disease and nucleosome concentrations increased with the stage of the disease.
Conclusions: Plasma nucleosome concentrations are a reliable way to differentiate dogs with hemangiosarcoma from healthy dogs. Further testing is underway to better characterize cancer associated HSA circulating nucleosomes and optimize future diagnostics for canine HSA detection.
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http://dx.doi.org/10.1186/s12917-021-02934-6 | DOI Listing |
Establishing the anterior-posterior body axis is a fundamental process during embryogenesis, and the fruit fly, , provides one of the best-known case studies of this process. In Drosophila, localized mRNA of serves as anterior determinant (AD). Bicoid engages in a concentration-dependent competition with nucleosomes and initiates symmetry-breaking along the AP axis by promoting chromatin accessibility at the loci of transcription factor (TF) genes that are expressed in the anterior of the embryo.
View Article and Find Full Text PDFACS Macro Lett
January 2025
Department of Physics, Kent State University, Kent, Ohio 44242, United States.
We investigate the impact of poly adenine (poly-A) sequences on the type and stability of liquid crystalline (LC) phases formed by concentrated solutions of gapped DNA (two duplex arms bridged by a flexible single strand) using synchrotron small-angle X-ray scattering and polarizing optical microscopy. While samples with mixed sequence form layered (smectic) phases, poly-A samples demonstrate a columnar phase at lower temperatures (5-35 °C), not previously observed in GDNA samples, and a smectic-B phase of exceptional stability at higher temperatures (35-65 °C). We present a model that connects the formation of these LC phases with the unique characteristics of poly-A sequences, which manifest in various biological contexts, including DNA condensation and nucleosome formation.
View Article and Find Full Text PDFSci Rep
January 2025
Molecular Modeling and Simulation Team, Institute for Quantum Life Science, National Institutes for Quantum Science and Technology, 4-9-1, Anagawa, Inage-Ku, Chiba City, Chiba, 263-8555, Japan.
Sequence-dependent mechanical properties of DNA could play essential roles in nuclear processes by affecting histone-DNA interactions. Previously, we found that the DNA entry site of the first nucleosomes from the transcription start site (+ 1 nucleosome) in budding yeast enriches AA/TT steps, but not the exit site, and the biased presence of AA/TT in the entry site was associated with the transcription levels of yeast genes. Because AA/TT is a rigid dinucleotide step, we considered that AA/TT causes DNA unwrapping.
View Article and Find Full Text PDFJ Chem Phys
January 2025
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
Eukaryotic DNA is packaged in the cell nucleus into chromatin, composed of arrays of DNA-histone protein octamer complexes, the nucleosomes. Over the past decade, it has become clear that chromatin structure in vivo is not a hierarchy of well-organized folded nucleosome fibers but displays considerable conformational variability and heterogeneity. In vitro and in vivo studies, as well as computational modeling, have revealed that attractive nucleosome-nucleosome interaction with an essential role of nucleosome stacking defines chromatin compaction.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208, USA.
Transcription factors (TFs) regulate gene expression despite constraints from chromatin structure and the cell cycle. Here we examine the concentration-dependent regulation of by the Bicoid morphogen through a combination of quantitative imaging, mathematical modeling and epigenomics in embryos. By live imaging of MS2 reporters, we find that, following mitosis, the timing of transcriptional activation driven by the P2 ( P2) enhancer directly reflects Bicoid concentration.
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