Methylation of Q105 on histone H2A is part of a dynamic regulatory mechanism integrating metabolism with ribosome biogenesis through recruitment of Nhp2

Abstract

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, 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 signals from cell cycle, metabolic and proliferative states. Furthermore, we identify a first epigenetic reader of this modification, the ribonucleoprotein Nhp2, which specifically recognizes the methylation on H2AQ105. Based on functional and proteomic data we suggest that Nhp2 functions as an adapter to bridge the rDNA chromatin with components of the small subunit processome and might help to efficiently coordinate transcription of rRNA with its post-transcriptional processing.