Histones are proteins that condense and structure the DNA of eukaryotic cell nuclei into units called nucleosomes. Their main functions are to compact DNA and regulate chromatin, therefore impacting gene regulation.
Histones H2A, H2B, H3 and H4 are known as the core histones, and they come together to form one nucleosome. The nucleosome core is formed of two H2A-H2B dimers and a H3-H4 tetramer.
In general, eukaryotic histones repress gene transcription, but It is now known that histones can be both positive and negative regulators of gene expression. These interactions are the basis of the histone code.
Histone Variants and Modifications
H2A may lack many the fancy tail modifications that have make H3 and H4 so popular in epigenetics. H2A has the most variants which give a dizzying array of diversity to nucleosome composition. H2A variants differ from each other mostly at their C-terminus which is responsible for intra-nucleosome binding and DNA binding. The acidic patch is also altered between variants, which is involved in higher order chromatin organization.
H2B forms a (H2A-H2B)-2 tetramer. This tetramer and it’s component dimers are easily exchanged in and out of the nucleosome compared to H3 and H4, meaning that the modifications on H2A and H2B are less likely to be maintained in chromatin
When you think H3K4, think activation. Whether it’s methylated or acetylated, this site will turn genes fasters than you can say PRDM9. Acylation of all histone residues are activating, and H3K4 is no exception. The real interest in H3K4 lies in its methylation.
H3K9 does double duty. It can turn genes on by getting acetylated, but can silence them just as easily when methylated. H3K9ac is a particularly important acetylation: it is highly correlated with active promoters. H3K9ac also has a high co-occurrence with H3K14ac and H3K4me3 which together are these three marks are the hallmark of active gene promoters
H3K27 is known for one thing: shutting down transcription. When H3K27 is trimethylated, it is tightly associated with inactive gene promoters. It acts in opposition to H3K4me3. Because of its dramatic and predictable effect on gene expression, H3K27me3 is a favorite of epigenesists looking for inactive genes.
H3K36 is like a fine wine: complex, intriguing, and an active source of interest among researchers. The modifications occurring at H3K36 are very diverse and don’t share much similarity with each other. They have roles in many important biological processes.
H4K5 is the closest lysine residue to the N-terminal tail of histone H4. Histone H4 forms a strong tetramer with histone H3. Like histone H3, H4 has a long N-terminal tail that is subject to various acetylations and methylations that are associated with many cellular processes. H4 modifications are not as well characterized as H3. H4 has much less sequence variation than the other histones across species; it seem to be structurally restrained by evolution likely due to important function
H4K8 is another lysine on that tail of histone H4 that doesn’t get a lot of attention. Like the others in this group, it is only known to be acetylated, it has not been shown to be methylated as of yet. This group of lysines are known to act as transcriptional activators. These lysines are also an excellent example of the histone code hypothesis in action.
H4K12 is yet another lysine on the N-terminal tail of histone H4 that yet again is acetylated and not methylated. Starting to sound familiar? Like H4K8ac, H4K12ac is part of a “backbone” of histone modifications that are associated with active promoters. H4K12ac is localized to the promoter, like other H4 acetylations; however, H4 localizes more to gene bodies than the other acetylations. This suggests that H4K8ac serves to facilitate transcriptional elongation.
H4K16 is part what should now be a familiar group of lysines on the N-terminal tail of histone H4. If you’ve been reading about the others, it should come as no surprise that H4K16 also is acetylated and not methylated. But wait; H4K16ac has some unique and interesting properties. Though H4K16ac is associated with transcriptional activation, it can also be linked with repression. The bromodomain of TIP5, part of NoRC, binds to H4K16ac. After binding, the NoRC complex serves to silence rDNA by recruiting HATs and DNMTs.
H4K20 if definitely the odd lysine out on the tail of H4. All the other lysines up until this point are acetylated and not methylated. H4K20 likes to go against the grain and is methylated but not acetylated. Like all lysine residues, H4K20 can be mono, di, or tri methylated. In the case of H4K20, these methylation states have different spatial disruptions and functions.