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. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wr ...

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 cell 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. 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 proteins and resembles thread wrapped around a spool. The nucleosome is the fundamen ...

s of the 'beads on a string' structure. Histone proteins are highly

post-translationally modified Post-translational modification (PTM) is the covalent and generally enzyme, enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by r ...

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 stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...

, 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 ami ...

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. 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 ...

and

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

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 − 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� ...

. 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 continue between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a role ...

(see

H3K9me2 H3K9me2 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the di-methylation at the 9th lysine residue of the histone H3 protein. H3K9me2 is strongly associated with transcriptional repression. H3 ...

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 H3K9me3 ...

), 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 acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl-CoA to form ε-''N''-acetyllysine. DNA is wrapped around histones, and, by transferring an ...

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

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

(see

H3K14ac H3K14ac is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the acetylation at the 14th lysine residue of the histone H3 protein. H3K14ac has not been widely studied partly due to previous lack of co ...

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. Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This structure consists of approximately 146 b ...

HIST1H3B Histone H3.1 is a protein that in humans is encoded by the ''HIST1H3B'' gene. Histones 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 ...

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 chromosomal fiber in eukaryotes. Two molecules of each of the four core hist ...

HIST1H3D Histone H3.1 is a protein that in humans is encoded by the ''HIST1H3D'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' ...

HIST1H3E Histone H3.1 is a protein that in humans is encoded by the ''HIST1H3E'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' ...

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 14 ...

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 Eukaryotes () are organisms whose cell ...

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 hist ...

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 fo ...

HIST1H3J Histone H3.1 is a protein that in humans is encoded by the ''HIST1H3J'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' ...

* 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 str ...

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 appr ...

, HIST2H3D * H3.3:

H3F3A Histone H3.3 is a protein that in humans is encoded by the ''H3F3A'' and ''H3F3B'' genes. It plays an essential role in maintaining genome integrity during mammalian development. Histones are basic nuclear proteins that are responsible for the n ...

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