Histones are the basic nuclear proteins responsible for the nucleosome structure of the chromosomal fiber. Five classes of histone genes have been reported, some of which are expressed only during S phase, while others are replication independent. The latter are referred to as replacement histones and are expressed in quiescent or terminally differentiated cells. H3F3B is one replacement histone [PMID: 8586426]. It constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Thereby it has a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability [PMID: 14718166, 15776021].