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- Title
Epigenetic rewriting at centromeric DNA repeats leads to increased chromatin accessibility and chromosomal instability.
- Authors
Decombe, Sheldon; Loll, François; Caccianini, Laura; Affannoukoué, Kévin; Izeddin, Ignacio; Mozziconacci, Julien; Escudé, Christophe; Lopes, Judith
- Abstract
Background: Centromeric 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. Results: Using 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. Conclusion: Our 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.
- Subjects
CHROMOSOMAL proteins; ARTIFICIAL chromosomes; HUMAN chromosomes; HISTONE demethylases; DNA; HISTONES; CHROMATIN
- Publication
Epigenetics & Chromatin, 2021, Vol 14, Issue 1, p1
- ISSN
1756-8935
- Publication type
Article
- DOI
10.1186/s13072-021-00410-x