Histone H3 is one of the five main

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

s involved in the structure of

chromatin Chromatin is a complex of DNA and protein found in eukaryote, 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 r ...

eukaryotic cell The eukaryotes ( ) constitute the domain of Eukaryota or Eukarya, organisms whose cells have a membrane-bound nucleus. All animals, plants, fungi, seaweeds, and many unicellular organisms are eukaryotes. They constitute a major group of Out ...

s. Featuring a main globular domain and a long N-terminal tail, H3 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, histone proteins and resembles thread wrapped around a bobbin, spool. The nucleosome ...

s of the 'beads on a string' structure. Histone proteins are highly post-translationally modified however Histone H3 is the most extensively modified of the five histones. The term "Histone H3" alone is purposely ambiguous in that it does not distinguish between sequence variants or modification state. Histone H3 is an important protein in the emerging field of

epigenetics In biology, epigenetics is the study of changes in gene expression that happen without changes to the DNA sequence. The Greek prefix ''epi-'' (ἐπι- "over, outside of, around") in ''epigenetics'' implies features that are "on top of" or "in ...

, where its sequence variants and variable modification states are thought to play a role in the dynamic and long term regulation of genes.

Epigenetics and post-translational modifications

The

N-terminus 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 amin ...

of H3 protrudes from the globular

core and is susceptible to post-translational modification that influence cellular processes. These modifications include the covalent attachment of methyl or acetyl groups to

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...

and

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...

amino acids and the phosphorylation of

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 − ...

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 when dissolved in water), a carboxyl group (which is in the deprotonated −COO− ...

. Di- and Tri-methylation of lysine 9 are associated with repression and

heterochromatin Heterochromatin is a tightly packed form of DNA or '' condensed DNA'', which comes in multiple varieties. These varieties lie on a continuum between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a rol ...

(see H3K9me2 and

H3K9me3 H3K9me3 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the tri-methylation at the 9th lysine residue of the histone H3 protein and is often associated with heterochromatin. Nomenclature H3K9me ...

), while mono-methylation of K4 (K4 corresponds to lysine residue at 4th position)(see

H3K4me1 H3K4me1 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the mono-methylation at the 4th lysine residue of the histone H3 protein and often associated with gene enhancers. Nomenclature H3K4me1 i ...

), is associated with active genes. Acetylation of histone H3 at several lysine positions in the histone tail is performed by

histone acetyltransferase Histone acetyltransferases (HATs) are enzymes that acetylation, acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl-CoA to form ε-N-acetyllysine, ε-''N''-acetyllysine. DNA is wrapped around his ...

enzymes (HATs). Acetylation of lysine14 is commonly seen in genes that are being actively transcribed into

RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

(see H3K14ac).

Sequence variants

Mammalian cells have seven known sequence variants of histone H3. These are denoted as Histone H3.1, Histone H3.2, Histone H3.3, Histone H3.4 (H3T), Histone H3.5, Histone H3.X and Histone H3.Y but have highly conserved sequences differing only by a few amino acids. Histone H3.3 has been found to play an important role in maintaining genome integrity during mammalian development. Histone variants from different organisms, their classification and variant specific features can be found i
"HistoneDB - with Variants"
database.

Genetics

Histone H3s are coded by several genes in the human genome, including: * H3.1:

HIST1H3A Histone H3.1 is a protein in humans that is encoded by the ''H3C1'' gene. Histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei and in most Archaeal phyla. ...

, HIST1H3B,

HIST1H3C Histone H3.1 is a protein that in humans is encoded by the ''HIST1H3C'' gene. Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosome, chromosomal fiber in eukaryotes. Two molecules of each of the ...

HIST1H3D Histone H3.1 is a protein that in humans is encoded by the ''HIST1H3D'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcri ...

HIST1H3E Histone H3.1 is a protein that in humans is encoded by the ''HIST1H3E'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcri ...

HIST1H3F Histone H3.1 is a protein that in humans is encoded by the ''HIST1H3F'' gene. Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This structure consists of approximately 1 ...

HIST1H3G Histone H3.1 is a protein that in humans is encoded by the ''HIST1H3G'' gene. Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryote The eukaryotes ( ) constitute the Doma ...

HIST1H3H Histone H3.1 is a protein that in humans is encoded by the ''HIST1H3H'' gene. Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core hi ...

HIST1H3I Histone H3.1 is a protein that in humans is encoded by the ''HIST1H3I'' gene. Function Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the f ...

HIST1H3J Histone H3.1 is a protein that in humans is encoded by the ''HIST1H3J'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcri ...

* H3.2:

HIST2H3A Histone cluster 2 H3 family member a is a protein that in humans is encoded by the HIST2H3A gene. Function Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This stru ...

HIST2H3C Histone H3.2 is a protein that in humans is encoded by the ''HIST2H3C'' gene. Function Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This structure consists of ap ...

, HIST2H3D * H3.3: H3F3A,

H3F3B Histone H3.3 is a protein that in humans is encoded by the ''H3-3A'', and the ''H3-3B'' genes. Function Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules ...

References

{{Chromo

Epigenetics and post-translational modifications

Sequence variants

Genetics

See also

References