Specifically, the ubiquitin on histone H2B opens up and unfolds regions of chromatin allowing transcription machinery access to the promoter and coding regions of DNA. While only a few isoforms of histone H2B have been studied in depth, researchers have found that histone H2B variants serve important roles. If certain variants stopped functioning, centromeres would not form correctly, genome integrity would be lost, and the DNA damage response would be silenced. Specifically, in some lower eukaryotes, a histone H2B variant binds to a histone H2A variant called H2AZ, localizes to active genes, and supports transcription in those regions. In mice, a variant called H2BE helps control the expression of olfactory genes. This supports the idea that isoforms of histone H2B may have specialized functions in different tissues. Isoforms There are sixteen variants of histone H2B found in humans, thirteen of which are expressed in regular body cells and three of which are only expressed in the testes. These variants, also called isoforms, are proteins that are structurally very similar to the regular histone H2B but feature some specific variations in their amino acid sequence. All variants of histone H2B contain the same number of amino acids, and the variations in sequence are few in number. Only two to five amino acids are changed, but even these small differences can alter the isoform’s, higher level structure. Histone H2B isoforms interact differently with other proteins, are found in specific regions of chromatin, have different types and numbers of post-translational modifications, and are more or less stable than regular histone H2B. All of these differences accumulate and cause the isoforms to have unique functions and even function differently in different tissues. Many histone H2B isoforms are expressed in a DNA replication independent manner. They are produced at the same level during all phases of the cell cycle. Regular histone H2B is only added to nucleosomes during the S-phase of the cell cycle when DNA is replicated; histone H2B isoforms can be added to nucleosomes at other times during the cell cycle. Histone variants of H2B can be explored using "HistoneDB with Variants" database. Post-Translational Modifications Histone H2B is modified by a combination of several types of post-translational modifications. These modifications affect the structural and functional organization of chromatin, and the majority of them are found outside the globular domain of the nucleosome where amino acid residues are more accessible. Possible modifications include acetylation,