Histones are nuclear proteins essential for the storage and organization of genomic DNA as chromatin. Chromatin consists of DNA wrapped tightly around histone oligomers to form nucleosomes. In addition to compacting the genome, histones also regulate the accessibility of the DNA to the transcription and replication machinery to influence gene expression and mitosis. In addition to the core histones H1, H2A, H2B, H3, and H4, there are histone variants with specific functions in gene expression, development, and DNA repair. One of the variants is HIST3H3, also known as H3.1t or H3t. The H3.1t protein is primarily expressed in the testis leading researchers to believe its main function is in DNA storage and compaction during spermatogenesis (1). Analysis of H3.1t containing nucleosomes revealed inherent instability compared to conventional nucleosomes (1). H3 and H3.1t are nearly identical by sequence however they differ structurally at a few key residues. For example, H3.1t contains valine at residue 111 which is responsible for the observed nucleosome instability (1). Valine 111 has been shown to be important for H3.1t deposition as well. The core histones are deposited by the chaperone Nap1, while H3.1t nucleosome assembly is mediated by an alternative histone chaperone, Nap2 (2). H3.1t has been found in small amounts in HeLa cell extracts as well suggesting a possible role in somatic cells (3). While the functions of H3.1t are still unknown, studies have used monoclonal H3.1t antibodies to investigate its biological role. In particular a H3.1t antibody specific for acetylated lysine 27 has proven to be a useful tool to uncover the epigenetic functions of H3.1t. One recent study identified a role for H3.1t in polycomb regulation (4). The researchers were able to identify an interaction between H3.1t and the PHD finger protein, PHF1 (4). They used H3.1t antibodies to demonstrate colocalization of H3.1t with PHF1 and uncover a potential interaction with the polycomb repressive pathway (4). Bioinformatic approaches have offered some interesting insight regarding diversification of H3 variants during speciation as well (5). Examining the role of H3 variants in tissue-specific gene expression among different species is just one of the interesting applications for H3.1t antibodies. Another potential application of H3.1t antibodies is in the investigation of fertility in men. Immunocytochemistry of spermatozoa has shown infertile men have an increased histone to protamine ratio which may influence chromatin structure (6).
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