CBP and Gcn5 drive zygotic genome activation independently of their catalytic 
activity

Ciabrelli, Filippo; Rabbani, Leily; Cardamone, Francesco; Zenk, Fides; Löser, Eva; Schächtle, Melanie A; Mazina, Marina; Loubiere, Vincent; Iovino, Nicola

doi:10.1126/sciadv.adf2687

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CBP and Gcn5 drive zygotic genome activation independently of their catalytic activity

MPG-Autoren

Ciabrelli, Filippo
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Rabbani, Leily
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Cardamone, Francesco
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Zenk, Fides
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Löser, Eva
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Schächtle, Melanie A
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Mazina, Marina
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Iovino, Nicola
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://www.science.org/doi/10.1126/sciadv.adf2687?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
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Zitation

Ciabrelli, F., Rabbani, L., Cardamone, F., Zenk, F., Löser, E., Schächtle, M. A., et al. (2023). CBP and Gcn5 drive zygotic genome activation independently of their catalytic activity. Science Advances, 9: eadf2687. doi:10.1126/sciadv.adf2687.

Zitierlink: https://hdl.handle.net/21.11116/0000-000D-12AB-E

Zusammenfassung

Zygotic genome activation (ZGA) is a crucial step of embryonic development. So far, little is known about the role of chromatin factors during this process. Here, we used an in vivo RNA interference reverse genetic screen to identify chromatin factors necessary for embryonic development in Drosophila melanogaster. Our screen reveals that histone acetyltransferases (HATs) and histone deacetylases are crucial ZGA regulators. We demonstrate that Nejire (CBP/EP300 ortholog) is essential for the acetylation of histone H3 lysine-18 and lysine-27, whereas Gcn5 (GCN5/PCAF ortholog) for lysine-9 of H3 at ZGA, with these marks being enriched at all actively transcribed genes. Nonetheless, these HATs activate distinct sets of genes. Unexpectedly, individual catalytic dead mutants of either Nejire or Gcn5 can activate zygotic transcription (ZGA) and transactivate a reporter gene in vitro. Together, our data identify Nejire and Gcn5 as key regulators of ZGA.