Inheritance of H3K9 methylation regulates genome architecture in Drosophila early embryos.

Constitutive Heterochromatin Early Embryogenesis H3K9 Methylation HP1a Clusters Intergenerational Inheritance

Journal

The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664

Informations de publication

Date de publication:
03 Jun 2024
Historique:
received: 28 02 2024
accepted: 15 04 2024
revised: 27 03 2024
medline: 4 6 2024
pubmed: 4 6 2024
entrez: 3 6 2024
Statut: aheadofprint

Résumé

Constitutive heterochromatin is essential for transcriptional silencing and genome integrity. The establishment of constitutive heterochromatin in early embryos and its role in early fruitfly development are unknown. Lysine 9 trimethylation of histone H3 (H3K9me3) and recruitment of its epigenetic reader, heterochromatin protein 1a (HP1a), are hallmarks of constitutive heterochromatin. Here, we show that H3K9me3 is transmitted from the maternal germline to the next generation. Maternally inherited H3K9me3, and the histone methyltransferases (HMT) depositing it, are required for the organization of constitutive heterochromatin: early embryos lacking H3K9 methylation display de-condensation of pericentromeric regions, centromere-centromere de-clustering, mitotic defects, and nuclear shape irregularities, resulting in embryo lethality. Unexpectedly, quantitative CUT&Tag and 4D microscopy measurements of HP1a coupled with biophysical modeling revealed that H3K9me2/3 is largely dispensable for HP1a recruitment. Instead, the main function of H3K9me2/3 at this developmental stage is to drive HP1a clustering and subsequent heterochromatin compaction. Our results show that HP1a binding to constitutive heterochromatin in the absence of H3K9me2/3 is not sufficient to promote proper embryo development and heterochromatin formation. The loss of H3K9 HMTs and H3K9 methylation alters genome organization and hinders embryonic development.

Identifiants

pubmed: 38831123
doi: 10.1038/s44318-024-00127-z
pii: 10.1038/s44318-024-00127-z
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : 192904750
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : EXC 2189
Organisme : EC | ERC | HORIZON EUROPE European Research Council (ERC)
ID : 819941

Informations de copyright

© 2024. The Author(s).

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Auteurs

Nazerke Atinbayeva (N)

Max Planck Institute of Immunobiology and Epigenetics, 79108, Freiburg im Breisgau, Germany.
Albert-Ludwigs-Universität Freiburg, Fahnenbergplatz, 79085, Freiburg im Breisgau, Germany.

Iris Valent (I)

Karlsruhe Institute of Technology (KIT), Zoological Institute, 76131, Karlsruhe, Germany.

Fides Zenk (F)

Brain Mind Institute, School of Life Sciences EPFL, SV3809, 1015, Lausanne, Switzerland.

Eva Loeser (E)

Max Planck Institute of Immunobiology and Epigenetics, 79108, Freiburg im Breisgau, Germany.

Michael Rauer (M)

Max Planck Institute of Immunobiology and Epigenetics, 79108, Freiburg im Breisgau, Germany.

Shwetha Herur (S)

Max Planck Institute of Immunobiology and Epigenetics, 79108, Freiburg im Breisgau, Germany.

Piergiuseppe Quarato (P)

San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.

Giorgos Pyrowolakis (G)

Centre for Biological signaling studies, University of Freiburg, 79104, Freiburg im Breisgau, Germany.

Alejandro Gomez-Auli (A)

Max Planck Institute of Immunobiology and Epigenetics, 79108, Freiburg im Breisgau, Germany.

Gerhard Mittler (G)

Max Planck Institute of Immunobiology and Epigenetics, 79108, Freiburg im Breisgau, Germany.

Germano Cecere (G)

Institute Pasteur, Mechanisms of Epigenetic Inheritance, Department of Developmental and Stem Cell Biology, UMR3738, CNRS, 75724, Cedex 15, Paris, France.

Sylvia Erhardt (S)

Karlsruhe Institute of Technology (KIT), Zoological Institute, 76131, Karlsruhe, Germany.

Guido Tiana (G)

Università degli Studi di Milano and INFN, Milan, Italy.

Yinxiu Zhan (Y)

Department of Experimental Oncology, European Institute of Oncology-IRCCS, Milan, Italy. yinxiu.zhan@ieo.it.

Nicola Iovino (N)

Max Planck Institute of Immunobiology and Epigenetics, 79108, Freiburg im Breisgau, Germany. iovino@ie-freiburg.mpg.de.

Classifications MeSH