In contrast to stably repressive, constitutive heterochromatin and stably 
active, euchromatin, facultative heterochromatin has the capacity to alternate 
between repressive and activated states of transcription. As such, it is an 
instructive source to understand the molecular basis for changes in chromatin 
structure that correlate with transcriptional status. Sirtuin 1 (SIRT1) and 
suppressor of variegation 3-9 homologue 1 (SUV39H1) are amongst the enzymes 
responsible for chromatin modulations associated with facultative 
heterochromatin formation. SUV39H1 is the principal enzyme responsible for the 
accumulation of histone H3 containing a tri-methyl group at its lysine 9 
position (H3K9me3) in regions of heterochromatin. SIRT1 is an NAD+-dependent 
deacetylase that targets histone H4 at lysine 16 (refs 3 and 4), and through an 
unknown mechanism facilitates increased levels of H3K9me3 (ref. 3). Here we show 
that the mammalian histone methyltransferase SUV39H1 is itself targeted by the 
histone deacetylase SIRT1 and that SUV39H1 activity is regulated by acetylation 
at lysine residue 266 in its catalytic SET domain. SIRT1 interacts directly 
with, recruits and deacetylates SUV39H1, and these activities independently 
contribute to elevated levels of SUV39H1 activity resulting in increased levels 
of the H3K9me3 modification. Loss of SIRT1 greatly affects SUV39H1-dependent 
H3K9me3 and impairs localization of heterochromatin protein 1. These findings 
demonstrate a functional link between the heterochromatin-related histone 
methyltransferase SUV39H1 and the histone deacetylase SIRT1.