%0 Journal Article %T Using synthetic genome readers/regulators to interrogate chromatin processes: A brief review. %A Philips SJ %A Danda A %A Ansari AZ %J Methods %V 225 %N 0 %D 2024 May 11 %M 38471600 %F 4.647 %R 10.1016/j.ymeth.2024.03.001 %X Aberrant gene expression underlies numerous human ailments. Hence, developing small molecules to target and remedy dysfunctional gene regulation has been a long-standing goal at the interface of chemistry and medicine. A major challenge for designing small molecule therapeutics aimed at targeting desired genomic loci is the minimization of widescale disruption of genomic functions. To address this challenge, we rationally design polyamide-based multi-functional molecules, i.e., Synthetic Genome Readers/Regulators (SynGRs), which, by design, target distinct sequences in the genome. Herein, we briefly review how SynGRs access chromatin-bound and chromatin-free genomic sites, then highlight the methods for the study of chromatin processes using SynGRs on positioned nucleosomes in vitro or disease-causing repressive genomic loci in vivo.