Nhp2 is a reader of H2AQ105me and part of a network integrating metabolism with rRNA synthesis

Ribosome biogenesis is an essential cellular process that requires integration of extracellular cues, such as metabolic state, with intracellular signaling, transcriptional regulation and chromatin accessibility at the ribosomal DNA. Here, we demonstrate that the recently identified histone modification, methylation of H2AQ105 (H2AQ105me), is an integral part of a dynamic chromatin network at the rDNA locus. Its deposition depends on a functional mTor signaling pathway as well as acetylation of histone H3 at position K56, thus integrating metabolic and proliferative signals.. Furthermore, we identify a first epigenetic reader of this modification, the ribonucleoprotein Nhp2, which specifically recognizes H2AQ105me. Based on functional and proteomic data we suggest that Nhp2 functions as an adapter to bridge rDNA chromatin with components of the small subunit processome to efficiently coordinate transcription of rRNA with its post-transcriptional processing. We support this by showing that an H2AQ105A mutant has a mild defect in early processing of rRNA.