Nucleosomes must be deacetylated behind elongating RNA polymerase II to prevent 
cryptic initiation of transcription within the coding region. RNA polymerase II 
signals for deacetylation through the methylation of histone H3 lysine 36 
(H3K36), which provides the recruitment signal for the Rpd3S histone deacetylase 
complex (HDAC). The recognition of methyl H3K36 by Rpd3S requires the 
chromodomain of its Eaf3 subunit. Paradoxically, Eaf3 is also a subunit of the 
NuA4 acetyltransferase complex, yet NuA4 does not recognize methyl H3K36 
nucleosomes. In Saccharomyces cerevisiae, we found that methyl H3K36 nucleosome 
recognition by Rpd3S also requires the plant homeobox domain (PHD) of its Rco1 
subunit. Thus, the coupled chromo and PHD domains of Rpd3S specify recognition 
of the methyl H3K36 mark, demonstrating the first combinatorial domain 
requirement within a protein complex to read a specific histone code.