Direct assessment of histone function using histone replacement

Histones serve many purposes in eukaryotic cells in the regulation of diverse genomic processes, including transcription, replication, DNA repair, and chro-matin organization. As such, experimental systems to assess histone function are fundamental resources toward elucidating the regulation of activities occur-ring 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 replace-ment 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.