PHF2-mediated H3K9me balance orchestrates heterochromatin stability and neural progenitor proliferation.

Autor:	Aguirre S; Department of Structural and Molecular Biology, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, 08028, Spain., Pappa S; Department of Structural and Molecular Biology, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, 08028, Spain., Serna-Pujol N; Department of Structural and Molecular Biology, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, 08028, Spain., Padilla N; Vall d'Hebron Institute of Research (VHIR), Passeig de la Vall d'Hebron, 119, E-08035, Barcelona, Spain., Iacobucci S; Department of Structural and Molecular Biology, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, 08028, Spain., Nacht AS; Center for Genomic Regulation (CRG), Barcelona Institute for Science and Technology (BIST), Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain., Vicent GP; Department of Structural and Molecular Biology, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, 08028, Spain., Jordan A; Department of Structural and Molecular Biology, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, 08028, Spain., de la Cruz X; Vall d'Hebron Institute of Research (VHIR), Passeig de la Vall d'Hebron, 119, E-08035, Barcelona, Spain.; Institut Català per la Recerca i Estudis Avançats (ICREA), Barcelona, 08018, Spain., Martínez-Balbás MA; Department of Structural and Molecular Biology, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, 08028, Spain. mmbbmc@ibmb.csic.es.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2024 Aug; Vol. 25 (8), pp. 3486-3505. Date of Electronic Publication: 2024 Jun 18.
DOI:	10.1038/s44319-024-00178-7
Abstrakt:	Heterochromatin stability is crucial for progenitor proliferation during early neurogenesis. It relays on the maintenance of local hubs of H3K9me. However, understanding the formation of efficient localized levels of H3K9me remains limited. To address this question, we used neural stem cells to analyze the function of the H3K9me2 demethylase PHF2, which is crucial for progenitor proliferation. Through mass-spectroscopy and genome-wide assays, we show that PHF2 interacts with heterochromatin components and is enriched at pericentromeric heterochromatin (PcH) boundaries where it maintains transcriptional activity. This binding is essential for silencing the satellite repeats, preventing DNA damage and genome instability. PHF2's depletion increases the transcription of heterochromatic repeats, accompanied by a decrease in H3K9me3 levels and alterations in PcH organization. We further show that PHF2's PHD and catalytic domains are crucial for maintaining PcH stability, thereby safeguarding genome integrity. These results highlight the multifaceted nature of PHF2's functions in maintaining heterochromatin stability and regulating gene expression during neural development. Our study unravels the intricate relationship between heterochromatin stability and progenitor proliferation during mammalian neurogenesis. (© 2024. The Author(s).)
Databáze:	MEDLINE
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