| Autor: |
Atinbayeva, Nazerke, Valent, Iris, Zenk, Fides, Loeser, Eva, Rauer, Michael, Herur, Shwetha, Quarato, Piergiuseppe, Pyrowolakis, Giorgos, Gomez-Auli, Alejandro, Mittler, Gerhard, Cecere, Germano, Erhardt, Sylvia, Tiana, Guido, Zhan, Yinxiu, Iovino, Nicola |
| Předmět: |
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| Zdroj: |
EMBO Journal; Jul2024, Vol. 43 Issue 13, p2685-2714, 30p |
| Abstrakt: |
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. Synopsis: Constitutive heterochromatin is crucial for transcriptional silencing and maintaining genome integrity. H3K9me3, a histone modification, is a key component of constitutive heterochromatin. This study explores how H3K9me3 is inherited from the maternal oocyte to the embryo, facilitating the transmission of epigenetic information from one generation to the next. Maternally inherited H3K9me3 is required for early embryogenesis in Drosophila. Maternally inherited H3K9me3 is maintained throughout early embryogenesis. HP1a binding is established independently of H3K9me3. The formation of HP1a foci is dependent on H3K9me3. Maternally inherited H3K9me3 guides HP1a clustering in early embryos and is essential for early fly embryogenesis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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