Glutamine methylation in histone H2A is an RNA-polymerase-I-dedicated modification

Abstract

Nucleosomes are decorated with numerous post-translational modifications capable of influencing many DNA processes1. Here, we describe a new class of histone modification, methylation of glutamine, occurring on yeast histone H2A at position 105 (Q105) and human H2A at Q104. We identify Nop1 as the methyltransferase in yeast and demonstrate that Fibrillarin is the ortholog enzyme in human cells. Glutamine methylation of H2A is restricted to the nucleolus. Global analysis in yeast, using an H2AQ105me specific antibody, show that this modification is exclusively enriched over the 35S rDNA transcriptional unit. We show that the Q105 residue is part of the binding site for the histone chaperone FACT (Facilitator of Transcription) complex2. Methylation of Q105 or its substitution to alanine disrupts binding to FACT in vitro. A yeast strain mutated at Q105 exhibits reduced histone incorporation and increased transcription at the rDNA locus. These features are phenocopied by mutations in FACT complex components. Together these data identify glutamine methylation of H2A as the first histone epigenetic mark dedicated to a specific RNA polymerase and define its function as a regulator of FACT interaction with nucleosomes.