RNA polymerase I (Pol I) is the only nuclear RNA polymerase dedicated exclusively to synthesizing rRNA, which is transcribed in the nucleolus as a single 35S RNA precursor. Now, Kouzarides and colleagues describe a modification of histone H2A that is unique to the 35S transcription unit and that has a Pol I–specific regulatory function. A survey of MS datasets to examine the prevalence of glutamine methylation within histones revealed a single site on Saccharomyces cerevisiae H2A, Q105, that was also detected on human H2A Q104. The Q105 methyltransferase activity was purified from yeast lysates and conclusively identified as the rRNA methyltransferase Nop1 by gene knockout; in vitro assays using recombinant protein confirmed the findings. Knockdown of Fibrillarin, the human Nop1 homolog, reduced H2A Q104 methylation in nucleoli of human cells. Transcription-inhibition assays showed that methylation of Q104 or Q105 requires active Pol I transcription. Intriguingly, Q105 is located in a region of H2A that is recognized by FACT, a nucleosome-remodeling complex that facilitates transcription elongation through chromatin. The authors show that methylation or alanine substitution of Q105 reduces H2A-peptide binding by FACT in vitro and that Q105A enhances transcription of reporters inserted into the yeast rRNA gene locus. Mutations that reduce FACT protein levels mimic the effects of Q105A, suggesting that methylation-responsive Q105-FACT interactions regulate Pol I activity within the rRNA transcription unit. Indeed, overexpressing Nop1 to increase Q105 methylation reduces FACT levels at the rRNA locus, thus revealing how glutamine methylation may modulate chromatin configuration to couple rRNA synthesis to the demands of cell growth. (Nature doi:10.1038/nature12819, 18 December 2013)