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 signalling, 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 signalling pathway and 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.

Automated summary

Ribosome biogenesis is a complex cellular process that involves integration of extracellular cues, such as metabolic state and intracellular signaling, transcriptional regulation, and chromatin accessibility at the ribosomal DNA. The recently identified histone modification, methylation of H2AQ105 (H2AQ105me), plays a key role in this process, dependent on the mTor signaling pathway and acetylation of histone H3. The ribonucleoprotein Nhp2 acts as an epigenetic reader of this modification, bridging rDNA chromatin with components of the small subunit processome to coordinate transcription of rRNA with its post-transcriptional processing.