A model of the nucleosome core is proposed based on a topologically linear array of histones attached sequentially to DNA. The linear complex folds helically forming a spring-like particle. Different variants of the particle are discussed (cylindrical springs with and without histone-histone contacts between turns of the helix, solenoidal spring). The model is consistent with known data about the nucleosome structure. Histones H3 and H4 have a special role in the model which is related also to the superstructure of chromatin.
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http://dx.doi.org/10.1093/nar/5.4.1371 | DOI Listing |
Nat Struct Mol Biol
January 2025
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Transcription activators are said to stimulate gene expression by 'recruiting' coactivators, yet this vague term fits multiple kinetic models. To directly analyze the dynamics of activator-coactivator interactions, single-molecule microscopy was used to image promoter DNA, a transcription activator and the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex within yeast nuclear extract. SAGA readily but transiently binds nucleosome-free DNA without an activator, while chromatin association occurs primarily when an activator is present.
View Article and Find Full Text PDFClin Transl Med
January 2025
BOE Technology Group Co., Ltd, Beijing, China.
Background: Multi-omics features of cell-free DNA (cfDNA) can effectively improve the performance of non-invasive early diagnosis and prognosis of cancer. However, multimodal characterization of cfDNA remains technically challenging.
Methods: We developed a comprehensive multi-omics solution (COMOS) to specifically obtain an extensive fragmentomics landscape, presented by breakpoint characteristics of nucleosomes, CpG islands, DNase clusters and enhancers, besides typical methylation, copy number alteration of cfDNA.
Nat Commun
January 2025
Friedrich Miescher Institute for Biomedical Research, Fabrikstrasse 24, 4056, Basel, Switzerland.
In the germ line and during early embryogenesis, DNA methylation (DNAme) undergoes global erasure and re-establishment to support germ cell and embryonic development. While DNAme acquisition during male germ cell development is essential for setting genomic DNA methylation imprints, other intergenerational roles for paternal DNAme in defining embryonic chromatin are unknown. Through conditional gene deletion of the de novo DNA methyltransferases Dnmt3a and/or Dnmt3b, we observe that DNMT3A primarily safeguards against DNA hypomethylation in undifferentiated spermatogonia, while DNMT3B catalyzes de novo DNAme during spermatogonial differentiation.
View Article and Find Full Text PDFJ Chem Phys
January 2025
Department of Physics and Astronomy and Center for Quantitative Biology, Rutgers University, Piscataway, New Jersey 08854, USA.
Nucleosomes are fundamental units of chromatin in which a length of genomic DNA is wrapped around a histone octamer spool in a left-handed superhelix. Large-scale nucleosome maps show a wide distribution of DNA wrapping lengths, which in some cases are tens of base pairs (bp) shorter than the 147 bp canonical wrapping length observed in nucleosome crystal structures. Here, we develop a thermodynamic model that assumes a constant free energy cost of unwrapping a nucleosomal bp.
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.
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