Histone H2B is one of the 5 main

histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wr ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

s involved in the structure of

chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

cells. Featuring a main globular domain and long

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

and

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

tails, H2B is involved with the structure of the

nucleosome A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundamen ...

Structure

Histone tails and their function in chromatin formation

Histone H2B is a lightweight structural protein made of 126

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s. Many of these

s have a positive charge at cellular pH, which allows them to interact with the negatively charged phosphate groups in DNA. Along with a central globular domain, histone H2B has two flexible histone tails that extend outwards – one at the N-terminal end and one at C-terminal end. These are highly involved in condensing

from the beads-on-a-string conformation to a 30-nm fiber. Similar to other

s, histone H2B has a distinct

histone fold A histone fold is a structurally conserved Structural motif, motif found near the C-terminus in every core histone sequence in a histone octamer responsible for the binding of histones into heterodimers. The histone fold averages about 70 amino aci ...

that is optimized for histone-histone as well as histone-DNA interactions. Two copies of histone H2B come together with two copies each of

histone H2A Histone H2A is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. The other histone proteins are: H1, H2B, H3 and H4. Background Histones are proteins that package DNA into nucleosomes. Hist ...

histone H3 Histone H3 is one of the five main histones involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H3 is involved with the structure of the nucleosomes of the 'beads on a stri ...

, and

histone H4 Histone H4 is one of the five main histone proteins involved in the structure of chromatin in eukaryote, eukaryotic cells. Featuring a main globular domain and a long N-terminus, N-terminal tail, H4 is involved with the structure of the nucleos ...

to form the octamer core of the nucleosome to give structure to DNA. To facilitate this formation, histone H2B first binds to

to form a heterodimer. Two of these heterodimers then bind together with a heterotetramer made of

and

, giving the

its characteristic disk shape. DNA is then wrapped around the entire nucleosome in groups of approximately 160 base pairs of DNA. The wrapping continues until all

has been packaged with the nucleosomes.

Function

Histone H2B is a structural

that helps organize eukaryotic DNA. It plays an important role in the biology of the

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucle ...

where it is involved in the packaging and maintaining of

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

s, regulation of

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

, and replication and

repair The technical meaning of maintenance involves functional checks, servicing, repairing or replacing of necessary devices, equipment, machinery, building infrastructure, and supporting utilities in industrial, business, and residential installa ...

of DNA. Histone H2B helps regulate

structure and function through post-translational modifications and specialized histone variants. Acetylation and

ubiquitin Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...

ation are examples of two post-translational modifications that affect the function of histone H2B in particular ways. Hyperacetylation of histone tails helps

DNA-binding protein DNA-binding proteins are proteins that have DNA-binding domains and thus have a specific or general affinity for DNA#Base pairing, single- or double-stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove ...

s access

by weakening histone-DNA and nucleosome-nucleosome interactions. Furthermore, acetylation of a specific

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...

residue binds to bromine-containing domains of certain

and chromatin regulatory

s. This docking facilitates the recruitment of these proteins to the correct region of the

. Ubiquitinated histone H2B is often found in regions of active transcription. Through the facilitation of

chromatin remodeling Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out ...

, it stimulates transcriptional elongation and sets the stage for further modifications that regulate multiple elements of transcription. Specifically, the ubiquitin on histone H2B opens up and unfolds regions of

allowing

machinery access to the promoter and coding regions of DNA. While only a few

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...

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

eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

s, a histone H2B variant binds to a

variant called H2AZ, localizes to active

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

s, and supports

in those regions. In mice, a variant called H2BE helps control the expression of olfactory

s. This supports the idea that

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

, are proteins that are structurally very similar to the regular histone H2B but feature some specific variations in their

sequence. All variants of histone H2B contain the same number of

s, and the variations in sequence are few in number. Only two to five

s are changed, but even these small differences can alter the isoform’s, higher level structure. Histone H2B isoforms interact differently with other

s, are found in specific regions of

, 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

to have unique functions and even function differently in different tissues. Many histone H2B

are expressed in a

DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritanc ...

independent manner. They are produced at the same level during all phases of the

cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

. Regular histone H2B is only added to

s during the

S-phase S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during ...

of the

when DNA is replicated; histone H2B

can be added to

s at other times during the

. Histone variants of H2B can be explored usin
"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

, and the majority of them are found outside the globular domain of the

where

residues are more accessible. Possible modifications include acetylation, 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

s contain specific patterns of hyperacetylation and hypoacetylation on certain

residues found in the N-terminal tail. Acetylation relies on specific

acetyltransferases that work at gene promoters during transcriptional activation. Adding an acetyl group to

residues in one of several positions in the

tail contributes to the activation of

. In fact, scientists consider acetylation of histone H2B’s N-terminal tails, such as

H2BK5ac H2BK5ac is an epigenetic modification to the DNA packaging protein Histone H2B. It is a mark that indicates the acetylation at the 5th lysine residue of the histone H2B protein. H2BK5ac is involved in maintaining stem cells and colon cancer. L ...

, to be an extremely important part of regulating

''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 Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...

threonine Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COO� ...

residue activates

. When a cell experiences metabolic stress, an

AMP-activated protein kinase 5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme (EC 2.7.11.31) that plays a role in cellular energy homeostasis, largely to activate glucose and fatty acid uptake and oxidation when cell ...

phosphorylates the

at position 36 in histone H2B of the promoter and coding regions on DNA, which helps regulate transcriptional elongation. If cells receive multiple

apoptotic Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes includ ...

stimuli, caspase-3 activates the Mst1 kinase, which phosphorylates the

at position 14 in all histone H2B proteins, which helps facilitate

chromatin condensation Prophase () is the first stage of cell division in both mitosis and meiosis. Beginning after interphase, DNA has already been replicated when the cell enters prophase. The main occurrences in prophase are the condensation of the chromatin reti ...

DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...

can induce this same response on a more localized scale very quickly to help facilitate

DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...

Ubiquitination

Ubiquitin residues are usually added to the

at position 120 on histone H2B. Ubiquitinating this

residue activates

. Scientists have discovered other ubiquitination sites in recent years, but they are not well studied or understood at this time. Ubiquitin-conjugating

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

s and ubiquitin

ligase In biochemistry, a ligase is an enzyme that can catalyze the joining (ligation) of two large molecules by forming a new chemical bond. This is typically via hydrolysis of a small pendant chemical group on one of the larger molecules or the enzym ...

s 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

. All ubiquitin moieties are removed from histone H2B during

metaphase Metaphase ( and ) is a stage of mitosis in the eukaryotic cell cycle in which chromosomes are at their second-most condensed and coiled stage (they are at their most condensed in anaphase). These chromosomes, carrying genetic information, align ...

and re-conjugated during

anaphase Anaphase () is the stage of mitosis after the process of metaphase, when replicated chromosomes are split and the newly-copied chromosomes (daughter chromatids) are moved to opposite poles of the cell. Chromosomes also reach their overall maxim ...

Genetics

Histone H2B’s

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

s, none of which contain

intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene. ...

s. All of these

s are located in

cluster 1 on

chromosome 6 Chromosome 6 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 6 spans more than 170 million base pairs (the building material of DNA) and represents between 5.5 and 6% of the total ...

and cluster 2 and cluster 3 on

chromosome 1 Chromosome 1 is the designation for the largest human chromosome. Humans have two copies of chromosome 1, as they do with all of the autosomes, which are the non-sex chromosomes. Chromosome 1 spans about 249 million nucleotide base pairs, which ar ...

. In each

cluster, histone H2B genes share a promoter region with sequences that code for

. While all

s in the

cluster are transcribed at high levels during

, individual histone H2B genes are also expressed at other times during the

. They are dually regulated by the cluster promoter sequences and their specific promoter sequences.

References

{{reflist Proteins DNA-binding proteins