%0 Journal Article %T Beyond the marks: reader-effectors as drivers of epigenetics and chromatin engineering. %A Franklin KA %A Shields CE %A Haynes KA %J Trends Biochem Sci %V 47 %N 5 %D 05 2022 %M 35427480 %F 14.264 %R 10.1016/j.tibs.2022.03.002 %X Chromatin is a system of proteins and DNA that regulates chromosome organization and gene expression in eukaryotes. Essential features that support these processes include biochemical marks on histones and DNA, 'writer' enzymes that generate or remove these marks and proteins that translate the marks into transcriptional regulation: reader-effectors. Here, we review recent studies that reveal how reader-effectors drive chromatin-mediated processes. Advances in proteomics and epigenomics have accelerated the discovery of chromatin marks and their correlation with gene states, outpacing our understanding of the corresponding reader-effectors. Therefore, we summarize the current state of knowledge and open questions about how reader-effectors impact cellular function and human disease and discuss how synthetic biology can deepen our knowledge of reader-effector activity.