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

Histone H3 lysine 9 methylation has been proposed to provide a major "switc h" for the functional organization of chromosomal subdomains. Here, we show that the murine Suv39h histone methyltransferases (HMTases) govern H3-K9 m ethylation at pericentric heterochromatin and induce a specialized histone methylation pattern that differs from the broad H3-K9 methylation present a t other chromosomal regions. Suv39h-deficient mice display severely impaire d viability and chromosomal instabilities that are associated with an incre ased 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.