Histone H3.1 combines with Histone H4 to form the H3/H4 tetramer. Two H2A/H2B heterodimers interact with an H3/H4 tetramer to form the histone octamer. Histone H3.1, an H3 variant that has thus far only been found in mammals, is replication dependent and is associated with gene activation and gene silencing. The tetramer is also modified by various enzymes and can act as a substrate for them. These modifications have been shown to be important in gene regulation. Because the histones are folded with their subunit partners, the tetramer may be a better substrate for specific enzymes and modifications.