This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Rsc4 is a subunit of the RSC, a chromatin remodeling complex, which plays a critical role in transcription by changing the position of histones relative to important pieces of the genome such as promotors or enhancers. It does this through the actions of an ATP utilizing motor subunit Sth1. The Sth1 activity can function on any nucleosome however, so several subunits of the RSC complex perform the task of selecting the appropriate nucleosomes for RSC. They do this by reading the post-translational modification pattern found primarily on the animo-terminal tails of the histone proteins within the nucleosome. The RSC complex contains more than half of the known bromodomains within the yeast cell and thus is sensitive to the acetylation pattern on chromatin. The tandem bromodomain (TBD) of Rsc4 is composed of two adjacent bromodomains. We would like to learn how the bromodomains function, that is, do they function as a single unit recognizing a single doubly acetylated peptide, or as two independent bromodomains. Structure determination of complexes with acetylated peptides will reveal the mode of recognition for TBD. We will examine which histone residues besides the acetyl-lysines are important for TBD binding. Understanding the function of this domain will also allow us to put this into the context of the larger biologically relevant RSC complex. For example is the Rsc4 TBD likely to be pointing in toward the nucleosome, as we suspect, or is it facilitating communication with other proteins, or both? Lastly, understanding the relationship between the structural and functional roles of Rsc4 will deepen our understaning of how large protein complexes, including the chromatin remodelling complexes, read the complex language of post-translational modifications found on chromatin.
Showing the most recent 10 out of 167 publications
