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In this issue of Molecular Cell, Behrens et al. (2021) address a long-standing challenge in the field of tRNA regulation and develop an approach for measuring tRNA abundance at unprecedented accuracy.Using a genetic platform to generate histone mutants in Drosophila, Regadas et al. (2021) discover a novel mechanism for tissue-specific gene expression requiring a chromatin state defined by acetylation of lysine 14 of H3 but lacking other activating histone post-translational modifications.Two recent papers, Rao et al. (2021), in this issue, and Sönmezer et a