Abstract
Histones serve many purposes in eukaryotic cells in the regulation of diverse genomic processes, including transcription, replication, DNA repair, and chromatin organization. As such, experimental systems to assess histone function are fundamental resources toward elucidating the regulation of activities occurring on chromatin. One set of important tools for investigating histone function are histone replacement systems, in which endogenous histone expression can be partially or completely replaced with a mutant histone. Histone replacement systems allow systematic screens of histone regulatory functions and the direct assessment of functions for histone residues. In this review, we describe existing histone replacement systems in model organisms, the benefits and limitations of these systems, and opportunities for future research with histone replacement strategies.