Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability

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Abstract

Histone H3 lysine 9 methylation has been proposed to provide a major "switch" for the functional organization of chromosomal subdomains. Here, we show that the murine Suv39h histone methyltransferases (HMTases) govern H3-K9 methylation at pericentric heterochromatin and induce a specialized histone methylation pattern that differs from the broad H3-K9 methylation present at other chromosomal regions. Suv39h-deficient mice display severely impaired viability and chromosomal instabilities that are associated with an increased tumor risk and perturbed chromosome interactions during male meiosis. These in vivo data assign a crucial role for pericentric H3-K9 methylation in protecting genome stability, and define the Suv39h HMTases as important epigenetic regulators for mammalian development.

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Peters, A. H. F. M., O’Carroll, D., Scherthan, H., Mechtler, K., Sauer, S., Schöfer, C., … Jenuwein, T. (2001). Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell, 107(3), 323–337. https://doi.org/10.1016/S0092-8674(01)00542-6

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