CBP and Gcn5 Drive Zygotic Genome Activation Independently of Their Catalytic Activity

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2023 Apr 21

PMID 37083536

Authors

Filippo Ciabrelli

Leily Rabbani

Francesco Cardamone

Fides Zenk

Eva Loser

Melanie A Schachtle

Marina Mazina

Vincent Loubiere

Nicola Iovino

Affiliations

Soon will be listed here.

Abstract

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 . 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.

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References

Morgan M, Shilatifard A . Reevaluating the roles of histone-modifying enzymes and their associated chromatin modifications in transcriptional regulation. Nat Genet. 2020; 52(12):1271-1281. DOI: 10.1038/s41588-020-00736-4. View

McKay D, Klusza S, Penke T, Meers M, Curry K, McDaniel S . Interrogating the function of metazoan histones using engineered gene clusters. Dev Cell. 2015; 32(3):373-86. PMC: 4385256. DOI: 10.1016/j.devcel.2014.12.025. View

Colonnetta M, Abrahante J, Schedl P, Gohl D, Deshpande G . CLAMP regulates zygotic genome activation in Drosophila embryos. Genetics. 2021; 219(2). PMC: 8633140. DOI: 10.1093/genetics/iyab107. View

Gaskill M, Gibson T, Larson E, Harrison M . GAF is essential for zygotic genome activation and chromatin accessibility in the early embryo. Elife. 2021; 10. PMC: 8079149. DOI: 10.7554/eLife.66668. View

Murphy P, Wu S, James C, Wike C, Cairns B . Placeholder Nucleosomes Underlie Germline-to-Embryo DNA Methylation Reprogramming. Cell. 2018; 172(5):993-1006.e13. DOI: 10.1016/j.cell.2018.01.022. View

Dorighi K, Swigut T, Henriques T, Bhanu N, Scruggs B, Nady N . Mll3 and Mll4 Facilitate Enhancer RNA Synthesis and Transcription from Promoters Independently of H3K4 Monomethylation. Mol Cell. 2017; 66(4):568-576.e4. PMC: 5662137. DOI: 10.1016/j.molcel.2017.04.018. View

Pritchard D, Schubiger G . Activation of transcription in Drosophila embryos is a gradual process mediated by the nucleocytoplasmic ratio. Genes Dev. 1996; 10(9):1131-42. DOI: 10.1101/gad.10.9.1131. View

Haberle V, Stark A . Eukaryotic core promoters and the functional basis of transcription initiation. Nat Rev Mol Cell Biol. 2018; 19(10):621-637. PMC: 6205604. DOI: 10.1038/s41580-018-0028-8. View

Ludlam W, Taylor M, Tanner K, Denu J, Goodman R, Smolik S . The acetyltransferase activity of CBP is required for wingless activation and H4 acetylation in Drosophila melanogaster. Mol Cell Biol. 2002; 22(11):3832-41. PMC: 133831. DOI: 10.1128/MCB.22.11.3832-3841.2002. View

10.

Koromila T, Gao F, Iwasaki Y, He P, Pachter L, Gergen J . Odd-paired is a pioneer-like factor that coordinates with Zelda to control gene expression in embryos. Elife. 2020; 9. PMC: 7417190. DOI: 10.7554/eLife.59610. View

11.

Carre C, Szymczak D, Pidoux J, Antoniewski C . The histone H3 acetylase dGcn5 is a key player in Drosophila melanogaster metamorphosis. Mol Cell Biol. 2005; 25(18):8228-38. PMC: 1234334. DOI: 10.1128/MCB.25.18.8228-8238.2005. View

12.

Kwasnieski J, Orr-Weaver T, Bartel D . Early genome activation in is extensive with an initial tendency for aborted transcripts and retained introns. Genome Res. 2019; 29(7):1188-1197. PMC: 6633261. DOI: 10.1101/gr.242164.118. View

13.

Akimaru H, Chen Y, Dai P, Hou D, Nonaka M, Smolik S . Drosophila CBP is a co-activator of cubitus interruptus in hedgehog signalling. Nature. 1997; 386(6626):735-8. DOI: 10.1038/386735a0. View

14.

Torres-Zelada E, Weake V . The Gcn5 complexes in Drosophila as a model for metazoa. Biochim Biophys Acta Gene Regul Mech. 2020; 1864(2):194610. DOI: 10.1016/j.bbagrm.2020.194610. View

15.

Liao Y, Smyth G, Shi W . featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2013; 30(7):923-30. DOI: 10.1093/bioinformatics/btt656. View

16.

Bonasio R, Shiekhattar R . Regulation of transcription by long noncoding RNAs. Annu Rev Genet. 2014; 48:433-55. PMC: 4285387. DOI: 10.1146/annurev-genet-120213-092323. View

17.

Dorafshan E, Kahn T, Glotov A, Savitsky M, Walther M, Reuter G . Ash1 counteracts Polycomb repression independent of histone H3 lysine 36 methylation. EMBO Rep. 2019; 20(4). PMC: 6446198. DOI: 10.15252/embr.201846762. View

18.

Bhardwaj V, Heyne S, Sikora K, Rabbani L, Rauer M, Kilpert F . snakePipes: facilitating flexible, scalable and integrative epigenomic analysis. Bioinformatics. 2019; 35(22):4757-4759. PMC: 6853707. DOI: 10.1093/bioinformatics/btz436. View

19.

Ibarra-Morales D, Rauer M, Quarato P, Rabbani L, Zenk F, Schulte-Sasse M . Histone variant H2A.Z regulates zygotic genome activation. Nat Commun. 2021; 12(1):7002. PMC: 8636486. DOI: 10.1038/s41467-021-27125-7. View

20.

Perez-Montero S, Carbonell A, Moran T, Vaquero A, Azorin F . The embryonic linker histone H1 variant of Drosophila, dBigH1, regulates zygotic genome activation. Dev Cell. 2013; 26(6):578-90. DOI: 10.1016/j.devcel.2013.08.011. View