Hilton, I.B. et al. Nat. Biotechnol. 33, 510–517 (2015).

Kearns, N.A. et al. Nat. Methods 12, 401–403 (2015).

Conclusions about the regulatory function of epigenetic marks such as histone methylation and acetylation are largely based on statistical association with gene expression; deciphering the role an individual mark plays in gene regulation is more challenging. Two recent reports tackle the targeted modification of histones at specific loci using the clustered, regularly interspaced, short palindromic repeats (CRISPR) system. Kearns et al. inactivate enhancers with a histone demethylase fused to nuclease-dead Cas9 (dCas9), and Hilton et al. target loci with an acetyltransferase-dCas9 fusion in order to regulate promoters and enhancers by activating transcription. Both approaches will allow a detailed understanding of the interplay between epigenetic modifications and gene expression.