The properties of centromeric nucleosomes have been the subject of considerable debate and controversy. Furuyama and Henikoff (2009) now provide surprising evidence that centromeric nucleosomes wrap DNA in an orientation that is opposite to that of canonical nucleosomes.
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Centromeric chromatin clearings demarcate the site of kinetochore formation.
Cell
January 2025
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Biochemistry, Biophysics, Chemical Biology Graduate Group, University of Pennsylvania, Philadelphia, PA, USA; Institute of Structural Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Penn Center for Genome Integrity, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:
The centromere is the chromosomal locus that recruits the kinetochore, directing faithful propagation of the genome during cell division. Using cryo-ET on human mitotic chromosomes, we reveal a distinctive architecture at the centromere: clustered 20- to 25-nm nucleosome-associated complexes within chromatin clearings that delineate them from surrounding chromatin. Centromere components CENP-C and CENP-N are each required for the integrity of the complexes, while CENP-C is also required to maintain the chromatin clearing.
View Article and Find Full Text PDFHigh-resolution analysis of human centromeric chromatin.
Life Sci Alliance
April 2025
National Cancer Institute, Center for Cancer Research, Laboratory of Receptor Biology and Gene Expression, Bethesda, MD, USA
Centromeres are marked by the centromere-specific histone H3 variant CENP-A/CENH3. Throughout the cell cycle, the constitutive centromere-associated network is bound to CENP-A chromatin, but how this protein network modifies CENP-A nucleosome conformations in vivo is unknown. Here, we purify endogenous centromeric chromatin associated with the CENP-C complex across the cell cycle and analyze the structures by single-molecule imaging and biochemical assays.
View Article and Find Full Text PDFPan-cancer analysis and single-cell analysis identifies the CENPN as a biomarker for survival prognosis and immunotherapy.
Discov Oncol
January 2025
Department of Oncology, Fuyang Hospital of Anhui Medical University, Fuyang, 236000, China.
Background: Centromere protein N (CENPN), located on chromosome 16q23.2, encodes vital nucleosome-associated complexes that are essential for dynamic assembly processes. CENPN plays a pivotal role in regulating cell proliferation and cell cycle progression by influencing mitotic events.
View Article and Find Full Text PDFStable centromere association of the yeast histone variant Cse4 requires its essential N-terminal domain.
EMBO J
January 2025
Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
Chromosome segregation relies on kinetochores that assemble on specialized centromeric chromatin containing a histone H3 variant. In budding yeast, a single centromeric nucleosome containing Cse4 assembles at a sequence-defined 125 bp centromere. Yeast centromeric sequences are poor templates for nucleosome formation in vitro, suggesting the existence of mechanisms that specifically stabilize Cse4 nucleosomes in vivo.
View Article and Find Full Text PDFNucleosome dynamics render heterochromatin accessible in living human cells.
bioRxiv
December 2024
Division of Developmental Biology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda MD 20892, USA.
The eukaryotic genome is packaged into chromatin, which is composed of a nucleosomal filament that coils up to form more compact structures. Chromatin exists in two main forms: euchromatin, which is relatively decondensed and enriched in transcriptionally active genes, and heterochromatin, which is condensed and transcriptionally repressed . It is widely accepted that chromatin architecture modulates DNA accessibility, restricting the access of sequence-specific, gene-regulatory, transcription factors to the genome.
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