Histones

What is a nucleosome?

A basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound in sequence around eight histone protein cores. H2A in yellow, H2B is red, H3 is blue and H4 is green. DNA is gray.

Tell me about Chromodomain

A chromodomain (chromatin organization modifier) is a protein structural domain of about 40-50 amino acid residues commonly found in proteins associated with the remodeling and manipulation of chromatin. The domain is highly conserved among both plants and animals, and is represented in a large number of different proteins in many genomes, such as that of the mouse. Some chromodomain-containing genes have multiple alternative splicing isoforms that omit the chromodomain entirely. In mammals, chromodomain-containing proteins are responsible for aspects of gene regulation related to chromatin remodeling and formation of heterochromatin regions. Chromodomain-containing proteins also bind methylated histones and appear in the RNA-induced transcriptional silencing complex. Picture: Structure of polycomb chromodomain

Comment on the turnover of the acetylation of histones

Acetylation of histones has a rapid turnover.

Tell me about H2A variants. How and where do H2A variants differ from each other?

H2A has the most variants, so has the widest array of diversity for 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.

Tell me about H2A.Bbd

H2A.Bbd (Barr body deficient) is mammal specific, and is the fastest evolving histone gene. It is believed be involved in opening chromatin structure, similar to acetylation

Tell me about H2B

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 modifications on H2A and H2B are less likely to be maintained in chromatin.

Tell me about H3K27

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.

Tell me about H3K36

H3K36 is currently a puzzle to researchers, an active source of interest. Modifications occurring at H3K36 are very diverse and don't share much similarity with each other.

Tell me about H3K9

H3K9 can both: turn on genes by getting acetylated, and silence them 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

H4K12

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

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

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.

Histone H4K5

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

Tell me about Histone H4K8

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.

What is HIRA?

HIRA is a histone chaperone. In particular HIRA has been linked to to transcription activation and is known to have an evolutionarily conserved role in heterochromatin formation.

What are histone chaperones?

Histone chaperones are histone binding proteins involved in the assembly of histones into nucleosomes and their activity has been used for the determination of chromatin structure and function.

What enzyme mediates the methylation of H3K27?

Histone methylase EZH2

List the 4 core histones

Histones H2A, H2B, H3 and H4 are known as the core histones, and they come together to form one nucleosome.

Basics: What are Histones?

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.

In H3K4, what does the K stand for?

Lysine

What is the nucleosome core formed from?

The nucleosome core is formed of two H2A-H2B dimers and a H3-H4 tetramer.

Tell me about the Universal H2A Variants

The universal H2A variants H2A.X and H2A.Z are found in almost all organisms. Phosphorylation of H2A.X at serine 139 (termed γ-H2A.X) is an early response to double strand breaks, leading to structural changes and eventually repair. H2A.Z has many roles, including transcriptional activation and repression and heterochromatin formation.

What happens if H3K27 is methylated?

Then genes around histone will be repressed

Tell me about Histone H3K4

When you see H3K4, think activation. Whether its methylated or acetylated, this site will turn genes faster that 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.