ArticleEpigenetics & chromatin2021
Epigenetic rewriting at centromeric DNA repeats leads to increased chromatin accessibility and chromosomal instability.
Article in Epigenetics & chromatin, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Contribution of histone variants to aneuploidy: a cancer perspective.Frontiers in genetics · 2023Pooled it
- Article
- Heterochromatin boundaries maintain centromere position, size and number.Nature structural & molecular biology · 2026Article
- Regulation of epigenetics and chromosome structure by human ORC2.Cell reports · 2025Article
- TASOR expression in naive embryonic stem cells safeguards their developmental potential.Cell reports · 2024Article
- Epigenetic frontiers: miRNAs, long non-coding RNAs and nanomaterials are pioneering to cancer therapy.Epigenetics & chromatin · 2024Review
- PHF2-mediated H3K9me balance orchestrates heterochromatin stability and neural progenitor proliferation.EMBO reports · 2024Article
- Genome-wide repeat landscapes in cancer and cell-free DNA.Science translational medicine · 2024Article
- Diverse heterochromatin states restricting cell identity and reprogramming.Trends in biochemical sciences · 2023Review
- Human centromere repositioning activates transcription and opens chromatin fibre structure.Nature communications · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCentromeric regions of human chromosomes contain large numbers of tandemly repeated α-satellite sequences. These sequences are covered with constitutive heterochromatin which is enriched in trimethylation of histone H3 on lysine 9 (H3K9me3). Although well studied using artificial chromosomes and global perturbations, the contribution of this epigenetic mark to chromatin structure and genome stability remains poorly known in a more natural context.
resultsUsing transcriptional activator-like effectors (TALEs) fused to a histone lysine demethylase (KDM4B), we were able to reduce the level of H3K9me3 on the α-satellites repeats of human chromosome 7. We show that the removal of H3K9me3 affects chromatin structure by increasing the accessibility of DNA repeats to the TALE protein. Tethering TALE-demethylase to centromeric repeats impairs the recruitment of HP1α and proteins of Chromosomal Passenger Complex (CPC) on this specific centromere without affecting CENP-A loading. Finally, the epigenetic re-writing by the TALE-KDM4B affects specifically the stability of chromosome 7 upon mitosis, highlighting the importance of H3K9me3 in centromere integrity and chromosome stability, mediated by the recruitment of HP1α and the CPC.
conclusionOur cellular model allows to demonstrate the direct role of pericentromeric H3K9me3 epigenetic mark on centromere integrity and function in a natural context and opens interesting possibilities for further studies regarding the role of the H3K9me3 mark.
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