Project 2
Remodeler: Targeting and Function
A central question is how remodelers select particular nucleosomes to remodel. Maggie Kasten and Alisha Schlichter are studying the proteins in RSC that bear bromodomains, motifs that bind acetylated histone tails. Kasten has recently determined that Rsc4 binds to the histone H3 tail acetylated at two positions. Our collaboration with Christopher Hill’s lab (University of Utah) has yielded the crystal structure of the Rsc4 tandem bromodomain bound to the H3 tail. Because RSC contains six additional bromodomains, it may serve as an important model complex for understanding how a remodeler can "read" combinations of acetylation modifications on histone tails. (This work is supported in part by a grant from the National Institutes of Health.) The SWR1 complex restructures nucleosomes, replacing a canonical histone (H2A) with a histone variant. To understand Htz1 function, we recently published the entire Htz1 genome and demonstrated that this histone variant promotes transcription at gene promoters by helping to expose promoter DNA to the transcriptional machinery. We are now determining whether remodelers like RSC eject nucleosomes bearing Htz1 to facilitate promoter exposure. (This work is supported in part by Huntsman Cancer Institute.)
