Histones are basic nuclear proteins responsible for nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. In vivo, histones are wrapped around by DNA in chromatin. Therefore, nucleosomes are more physiologically relevant substrates than histones and histone-derived peptides for in vitro studies. More importantly, some histone methyltransferases are significantly more active, as well as specific, when using nucleosomal substrates in HMT assays, such as DOT1L and NSD family enzymes. Nucleosomes are also widely used in histone methyltransferase screening assays to identify small molecular inhibitors for drug discovery. The called linker histone, H1, binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. So it is necessary for the condensation of nucleosome chains into higher-order structured fibers. It can also act as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation. Histone H1.2 is a replication-dependent histone that is a member of the histone H1 family.