Several lines of recent evidence support a role for chromatin in splicing 
regulation. Here, we show that splicing can also contribute to histone 
modification, which implies bidirectional communication between epigenetic 
mechanisms and RNA processing. Genome-wide analysis of histone methylation in 
human cell lines and mouse primary T cells reveals that intron-containing genes 
are preferentially marked with histone H3 Lys36 trimethylation (H3K36me3) 
relative to intronless genes. In intron-containing genes, H3K36me3 marking is 
proportional to transcriptional activity, whereas in intronless genes, H3K36me3 
is always detected at much lower levels. Furthermore, splicing inhibition 
impairs recruitment of H3K36 methyltransferase HYPB (also known as Setd2) and 
reduces H3K36me3, whereas splicing activation has the opposite effect. Moreover, 
the increase of H3K36me3 correlates with the length of the first intron, 
consistent with the view that splicing enhances H3 methylation. We propose that 
splicing is mechanistically coupled to recruitment of HYPB/Setd2 to elongating 
RNA polymerase II.