Histone H2B

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Histone H2B is one of the 5 main

C-terminal tails, H2B is involved with the structure of the nucleosomes.[1]

Structure

Histone tails and their function in chromatin formation

Histone H2B is a lightweight structural protein made of 126 amino acids.[2] Many of these amino acids have a positive charge at cellular pH, which allows them to interact with the negatively charged phosphate groups in DNA.[3] Along with a central globular domain, histone H2B has two[verification needed] flexible histone tails that extend outwards – one at the N-terminal end and one at C-terminal end. These are highly involved in condensing chromatin from the beads-on-a-string conformation to a 30-nm fiber.[3] Similar to other histone proteins, histone H2B has a distinct histone fold that is optimized for histone-histone as well as histone-DNA interactions.[1]

Two copies of histone H2B come together with two copies each of histone H2A, histone H3, and histone H4 to form the octamer core of the nucleosome[2] to give structure to DNA.[3] To facilitate this formation, histone H2B first binds to histone H2A to form a heterodimer.[2] Two of these heterodimers then bind together with a heterotetramer made of histone H3 and histone H4, giving the nucleosome its characteristic disk shape.[3] DNA is then wrapped around the entire nucleosome in groups of approximately 160 base pairs of DNA.[1] The wrapping continues until all chromatin has been packaged with the nucleosomes.[4]

Function

Basic units of chromatin structure

Histone H2B is a structural

transcription, and replication and repair of DNA.[2] Histone H2B helps regulate chromatin structure and function through post-translational modifications and specialized histone variants.[4]

Acetylation and

transcription machinery access to the promoter and coding regions of DNA.[7]

While only a few

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.[4]

DNA damage response

Ubiquitination of histone H2B in response to DNA damage is important for timely initiation of DNA repair.[8] Ubiquitinase RNF20/RNF40 specifically modifies histone H2B at position K120 and this modification is need for recruitment to damaged DNA of the factors necessary for repair by the pathways of homologous recombination and non-homologous end joining.[8]

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.[4] 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.[4]

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.[4]

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.[4] 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.[1] These modifications affect the structural and functional organization of chromatin,[9] and the majority of them are found outside the globular domain of the nucleosome where amino acid residues are more accessible.[7] Possible modifications include acetylation, methylation, phosphorylation, ubiquitination, and sumoylation.[9] Acetylation, phosphorylation, and ubiquitination are the most common and most studied modifications of histone H2B.

Acetylation

Histone H2B proteins found both in the

transcription.[9]

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.[10]

Phosphorylation

In histone H2B, a phosphorylated

transcriptional elongation.[2] 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.[2]

Ubiquitination

Ubiquitin residues are usually added to the

transcription.[3] Scientists have discovered other ubiquitination sites in recent years, but they are not well studied or understood at this time.[4] 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.[7]

Genetics

Histone H2B’s

chromosome 1. In each gene cluster, histone H2B genes share a promoter region with sequences that code for histone H2A. While all genes in the histone cluster are transcribed at high levels during S-phase, individual histone H2B genes are also expressed at other times during the cell cycle. They are dually regulated by the cluster promoter sequences and their specific promoter sequences.[4]

See also

References

  1. ^
    PMID 16472024
    .
  2. ^
    PMID 26359231
    .
  3. ^
    ISBN 978-1-4292-3413-9
    .
  4. ^
    PMID 25922622
    .
  5. ^
    PMID 26343795
    .
  6. ^ a b c "Histone H2B (53H3) Mouse mAb #2934". Cell Signaling Technology. Retrieved 24 November 2015.
  7. ^
    PMID 16772277
    .
  8. ^ a b Uckelmann M, Sixma TK. Histone ubiquitination in the DNA damage response. DNA Repair (Amst). 2017 Aug;56:92-101. doi: 10.1016/j.dnarep.2017.06.011. Epub 2017 Jun 9. PMID: 28624371
  9. ^
    S2CID 25071586
    .
  10. PMID 22121020
    .
  11. ^ Khare SP, Habib F, Sharma R, Gadewal N, Gupta S, Galande S. "Histone H2B". HIstome: A Relational Knowledgebase of Human Proteins and Histone Modifying Enzymes. Nucleic Acids Research. Archived from the original on 16 October 2016. Retrieved 24 November 2015.
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