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Histone H3 lysine 9 methylation is an epigenetic imprint of facultative heterochromatin

Abstract

Post-translational modifications of histone amino termini are an important regulatory mechanism that induce transitions in chromatin structure, thereby contributing to epigenetic gene control and the assembly of specialized chromosomal subdomains1,2. Methylation of histone H3 at lysine 9 (H3–Lys9) by site-specific histone methyltransferases (Suv39h HMTases)3 marks constitutive heterochromatin4,5,6. Here, we show that H3–Lys9 methylation also occurs in facultative heterochromatin of the inactive X chromosome (Xi) in female mammals. H3–Lys9 methylation is retained through mitosis, indicating that it might provide an epigenetic imprint for the maintenance of the inactive state. Disruption of the two mouse Suv39h HMTases abolishes H3-Lys9 methylation of constitutive heterochromatin but not that of the Xi. In addition, HP1 proteins, which normally associate with heterochromatin, do not accumulate with the Xi. These observations suggest the existence of an Suv39h-HP1-independent pathway regulating H3-Lys9 methylation of facultative heterochromatin.

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Figure 1: H3–Lys9 methylation of the Barr body in human cells.
Figure 2: H3–Lys9 methylation of the Xi in mouse metaphase chromosomes.
Figure 3: Suv39h-independent H3–Lys9 methylation of the Xi and Y chromosomes in mouse bone-marrow spreads.
Figure 4: Absence of HP1 localization in the Barr body and the Xi chromosome.
Figure 5: HP1 fails to localize to Suv39h-independent H3–Lys9 methylation.

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Acknowledgements

We thank P.B. Singh for HP1β antibodies, P. Chambon for HP1α antibodies, B. Buendia for HP1α antibodies, and J. Fuchs and U. Waginger for help with immuno-FISH analysis. This work was supported by the IMP through Boehringer Ingelheim and by grants from the Vienna Economy Promotion Fund (T.J.), the Austrian Research Promotion Fund (D.S.) and the Medical Research Council, UK (J.E.M. and N.B.).

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Correspondence to Thomas Jenuwein.

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Peters, A., Mermoud, J., O'Carroll, D. et al. Histone H3 lysine 9 methylation is an epigenetic imprint of facultative heterochromatin. Nat Genet 30, 77–80 (2002). https://doi.org/10.1038/ng789

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