The Role of the Nucleosomal Acidic Patch in Histone Dimer Exchange
Authors
Gioacchini, NathanFaculty Advisor
Craig PetersonAcademic Program
Interdisciplinary Graduate ProgramUMass Chan Affiliations
Program in Molecular MedicineDocument Type
Doctoral DissertationPublication Date
2022-01-07
Metadata
Show full item recordAbstract
Eukaryotes organize their genomes by wrapping DNA around positively charged proteins called histones to form a structure known as chromatin. This structure is ideal for keeping the genome safe from damage, but also becomes an obstacle for the transcriptional machinery to access information stored in the DNA. To facilitate a balance between storage and accessibility, eukaryotes utilize a family of enzymes known as ATP-dependent chromatin remodelers to directly manipulate chromatin structure. The diverse activities of these chromatin remodeling enzymes range from simply sliding nucleosomes to reveal transcription start sites, to editing the composition of a nucleosome by exchanging canonical histones for histone variants. Chromatin remodeling enzymes recognize features of the nucleosome that activate their ATPase domains and enable proper remodeling function. One nuclear epitope that has been extensively studied is the nucleosomal acidic patch. This negatively charged region on the face of the nucleosome has been shown to be essential for remodeling enzymes like Chd1, ISWI, and INO80C. The chromatin remodeler SWR1C edits nucleosomes by removing the canonical histone H2A from nucleosomes and exchanges it for the histone variant H2A.Z, but the role of the acidic patch in this process has not been investigated. In this work, I showed that SWR1C has normal binding affinity to acidic patch mutant nucleosomes and retains ATPase stimulation but can no longer exchange dimers on this substrate. This work also identified a novel arginine anchor on the essential SWR1C subunit, Swc5, that binds specifically to the nucleosomal acidic patch. The data in this work suggest a mechanism where SWR1C engages nucleosomes and uses the Swc5 subunit to recognize the nucleosomal acidic patch to couple ATPase activity to histone dimer exchange.DOI
10.13028/5nky-nq39Permanent Link to this Item
http://hdl.handle.net/20.500.14038/31404Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/5nky-nq39