The mammalian genome contains numerous regions known as facultative 
heterochromatin, which contribute to transcriptional silencing during 
development and cell differentiation. We have analyzed the pattern of histone 
modifications associated with facultative heterochromatin within the mouse 
imprinted Snurf-Snrpn cluster, which is homologous to the human Prader-Willi 
syndrome genomic region. We show here that the maternally inherited Snurf-Snrpn 
3-Mb region, which is silenced by a potent transcription repressive mechanism, 
is uniformly enriched in histone methylation marks usually found in constitutive 
heterochromatin, such as H4K20me3, H3K9me3, and H3K79me3. Strikingly, we found 
that trimethylated histone H3 at lysine 36 (H3K36me3), which was previously 
identified as a hallmark of actively transcribed regions, is deposited onto the 
silenced, maternally contributed 3-Mb imprinted region. We show that H3K36me3 
deposition within this large heterochromatin domain does not correlate with 
transcription events, suggesting the existence of an alternative pathway for the 
deposition of this histone modification. In addition, we demonstrate that 
H3K36me3 is markedly enriched at the level of pericentromeric heterochromatin in 
mouse embryonic stem cells and fibroblasts. This result indicates that H3K36me3 
is associated with both facultative and constitutive heterochromatin. Our data 
suggest that H3K36me3 function is not restricted to actively transcribed regions 
only and may contribute to the composition of heterochromatin, in combination 
with other histone modifications.