ArticleEpigenetics & chromatin2017
Internal modifications in the CENP-A nucleosome modulate centromeric dynamics.
Article in Epigenetics & chromatin, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- Determinants of centromeric nucleosome conformation.bioRxiv : the preprint server for biology · 2026Article
- Linker histone H1.5 contributes to centromere integrity.Nucleic acids research · 2026Article
- Preserving centromere identity: right amounts of CENP-A at the right place and time.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2025Review
- High-resolution analysis of human centromeric chromatin.Life science alliance · 2025Article
- Recent updates of centromere proteins in hepatocellular carcinoma: a review.Infectious agents and cancer · 2025Review
- Molecular Dynamics Simulations of Nucleosomes Containing Histone Variant H2A.J.International journal of molecular sciences · 2024Article
- Native and tagged CENP-A histones are functionally inequivalent.Epigenetics & chromatin · 2024Article
- Article
- Centromere Chromatin Dynamics at a Glance.Epigenomes · 2022Review
- Centromere Identity and the Regulation of Chromosome Segregation.Frontiers in cell and developmental biology · 2022Review
- A glitch in the snitch: the role of linker histone H1 in shaping the epigenome in normal and diseased cells.Open biology · 2021Review
- Nano-Surveillance: Tracking Individual Molecules in a Sea of Chromatin.Journal of molecular biology · 2021Review
- Comparing DNA replication programs reveals large timing shifts at centromeres of endocycling cells in maize roots.PLoS genetics · 2020Article
- Conservation of centromeric histone 3 interaction partners in plants.Journal of experimental botany · 2020Article
- Epigenetic regulation of centromere function.Cellular and molecular life sciences : CMLS · 2020Review
- Review
- Minimal Cylinder Analysis Reveals the Mechanical Properties of Oncogenic Nucleosomes.Biophysical journal · 2020Article
- Priming chromatin for segregation: functional roles of mitotic histone modifications.Cell cycle (Georgetown, Tex.) · 2020Review
- Review
- Intrinsic elasticity of nucleosomes is encoded by histone variants and calibrated by their binding partners.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPosttranslational modifications of core histones are correlated with changes in transcriptional status, chromatin fiber folding, and nucleosome dynamics. However, within the centromere-specific histone H3 variant CENP-A, few modifications have been reported, and their functions remain largely unexplored. In this multidisciplinary report, we utilize in silico computational and in vivo approaches to dissect lysine 124 of human CENP-A, which was previously reported to be acetylated in advance of replication.
resultsComputational modeling demonstrates that acetylation of K124 causes tightening of the histone core and hinders accessibility to its C-terminus, which in turn diminishes CENP-C binding. Additionally, CENP-A K124ac/H4 K79ac containing nucleosomes are prone to DNA sliding. In vivo experiments using a CENP-A acetyl or unacetylatable mimic (K124Q and K124A, respectively) reveal alterations in CENP-C levels and a modest increase in mitotic errors. Furthermore, mutation of K124 results in alterations in centromeric replication timing. Purification of native CENP-A proteins followed by mass spectrometry analysis reveals that while CENP-A K124 is acetylated at G1/S, it switches to monomethylation during early S and mid-S phases. Finally, we provide evidence implicating the histone acetyltransferase (HAT) p300 in this cycle.
conclusionsTaken together, our data suggest that cyclical modifications within the CENP-A nucleosome contribute to the binding of key kinetochore proteins, the integrity of mitosis, and centromeric replication. These data support the paradigm that modifications in histone variants can influence key biological processes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.