During meiosis, paternal and maternal homologous chromosomes recombine at specific recombination sites named hotspots. What renders 2% of the mammalian genomes permissive to meiotic recombination by allowing Spo11 endonuclease to initiate double-strand breaks is largely unknown. Work in yeast has shown that chromatin accessibility seems to be important for this activity. Here, we define nucleosome profiles and dynamics at four mouse recombination hotspots by purifying highly enriched fractions of meiotic cells. We found that nucleosome occupancy is generally stable during meiosis progression. Interestingly, the cores of recombination hotspots have largely open chromatin structure, and the localization of the few nucleosomes present in these cores correlates precisely with the crossover-free zones in recombinogenic domains. Collectively, these high-resolution studies suggest that nucleosome occupancy seems to direct, at least in part, how meiotic recombination events are processed.
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http://dx.doi.org/10.1038/embor.2010.79 | DOI Listing |
Elife
January 2025
Translational Science and Therapeutics Division, Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States.
The association between late replication timing and low transcription rates in eukaryotic heterochromatin is well known, yet the specific mechanisms underlying this link remain uncertain. In , the histone deacetylase Sir2 is required for both transcriptional silencing and late replication at the repetitive ribosomal DNA (rDNA) arrays. We have previously reported that in the absence of , a de-repressed RNA PolII repositions MCM replicative helicases from their loading site at the ribosomal origin, where they abut well-positioned, high-occupancy nucleosomes, to an adjacent region with lower nucleosome occupancy.
View Article and Find Full Text PDFNat 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 PDFNat 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 PDFbioRxiv
December 2024
Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
A major challenge in epigenetics is uncovering the dynamic distribution of nucleosomes and other DNA-binding proteins, which plays a crucial role in regulating cellular functions. Established approaches such as ATAC-seq, ChIP-seq, and CUT&RUN provide valuable insights but are limited by the ensemble nature of their data, masking the cellular and molecular heterogeneity that is often functionally significant. Recently, long-read sequencing technologies, particularly Single Molecule, Real-Time (SMRT/PacBio) sequencing, have introduced transformative capabilities, such as N-methyladenine (6mA) footprinting.
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