The most basic unit of Eukaryotic nuclear packing is the nucleosome. At this level, DNA is wound around histone octamers; these repeating nucleosome units then wind around one another, amalgamating into chromatin. Though condensed heterochromatin is ideal for nuclear packing, it bars the binding of DNA‐mediating proteins such as polymerases. Therefore in eukaryotes, chromatin remodelers, proteins which relax the nucleosome unit to expose DNA transcripts, are necessary for mediation of vital genetic processes. These genetic implications for chromatin remodelers necessitate an understanding of their structure, and binding mechanism. This is a challenge in the case of RSC, a 17 subunit Saccharomyces cerevisiae chromatin remodeler. Due to its substantial size, its full, detailed structure remains undetermined. Additionally, the explicit mechanism behind RSC function, that is, where it binds to the nucleosome, and when this binding occurs has yet to be demonstrated. In this work, we aim to illuminate the structure/function relationship of the yeast RSC chromatin remodeler. The RSC complex exists in two mutually exclusive isoforms, differing only in one subunit, Rsc1 or Rsc2. We expect that the Rsc1/2 bromodomains are responsible for RSC‐nucleosome binding and that the acetylation of lysine is the sequestering mechanism. Therefore, exploiting the presence of bromodomains at these subunits, we utilize an expanded genetic code in yeast and a crosslinker unnatural amino acid to scan for histone‐Rsc1/2 nucleosomal contacts as a way to identify interfaces at the chromosomal level, in vivo. We scan specifically H3 and H4 due to their high level of lysine acetylation, and use confirmatory western‐blot to identify shifts indicative of successful cross‐linking. We believe that if we can illuminate all RSC‐nucleosome contact in this way that we can create a map of RSC active‐site binding, and can then investigate how this binding changes under varying physiological conditions.Support or Funding InformationResearch conducted with the support of PI Bryan Wilkins and Manhattan College Department of Chemistry.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.