Chromatin modifications are linked with regulating patterns of gene expression, but their causal role and context-dependent impact on transcription remains unresolved. Here, I will present a modular epigenome editing platform that enables nine key chromatin modifications – or combinations thereof – to be programmed to specific loci in living cells. By coupling such precision epigenome editing with single-cell readouts, we can systematically quantitate the magnitude and heterogeneity of transcriptional responses elicited by each specific chromatin modification. I will discuss how we use this to systematically dissect context-dependent interactions, define causal regulatory roles, and identify combinatorial effects (histone code?). Taken together, our precision epigenome-perturbation strategy helps to unveil the direct functions of chromatin modifications in genome regulation, and their interplay with other regulatory layers.