methylation, phosphorylation, ubiquitination, and sumoylation. Acetylation, phosphorylation, and ubiquitination are the most common and most studied modifications of histone H2B. Acetylation Histone H2B proteins found both in the promoter and coding regions of genes contain specific patterns of hyperacetylation and hypoacetylation on certain lysine residues found in the N-terminal tail. Acetylation relies on specific histone acetyltransferases that work at gene promoters during transcriptional activation. Adding an acetyl group to lysine residues in one of several positions in the amino acid tail contributes to the activation of transcription. In fact, scientists consider acetylation of histone H2B’s N-terminal tails, such as H2BK5ac, to be an extremely important part of regulating gene transcription. O-GlcNAcylation Modification of H2B S112 with O-GlcNAc is thought to facilitate monoubiquitination of K112, which in turn is associated with transcriptionally activated regions. Phosphorylation In histone H2B, a phosphorylated serine or threonine residue activates transcription. When a cell experiences metabolic stress, an AMP-activated protein kinase phosphorylates the lysine at position 36 in histone H2B of the promoter and coding regions on DNA, which helps regulate transcriptional elongation. If cells receive multiple apoptotic stimuli, caspase-3 activates the Mst1 kinase, which phosphorylates the serine at position 14 in all histone H2B proteins, which helps facilitate chromatin condensation. DNA damage can induce this same response on a more localized scale very quickly to help facilitate DNA repair. Ubiquitination Ubiquitin residues are usually added to the lysine at position 120 on histone H2B. Ubiquitinating this lysine residue activates transcription. Scientists have discovered other ubiquitination sites in recent years, but they are not well studied or understood at this time. Ubiquitin-conjugating enzymes and ubiquitin ligases regulate the ubiquitination of histone H2B. These enzymes use co-transcription to conjugate ubiquitin to histone H2B. Histone H2B’s level of ubiquitination varies throughout the cell cycle. All ubiquitin moieties are removed from histone H2B during metaphase and re-conjugated during anaphase. Genetics Histone H2B’s amino acid sequence is highly evolutionarily conserved. Even distantly related species have extremely similar histone H2B proteins. The histone H2B family contains 214 members from many different and diverse species. In humans, histone H2B is coded for by twenty-three different genes, none of which contain introns. All of these genes are located in histone cluster 1 on chromosome 6 and cluster 2 and cluster 3 on chromosome 1. In each gene cluster, histone H2B genes share a promoter region with sequences that code for histone H2A. While