Histone-Modifying Enzymes
Encyclopedia
The packaging of the eukaryotic genome
into highly condensed chromatin
makes it inaccessible to the factors required for gene transcription
, DNA replication, recombination
and repair. Eukaryotes have developed intricate mechanisms to overcome this repressive barrier imposed by the chromatin
. The nucleosome is composed of an octamer of the four core histone
s (H3, H4, H2A, H2B) around which 147 base pairs of DNA are wrapped. Several distinct classes of enzyme
can modify histone
s at multiple sites. The figure on the right enlists those histone-modifying enzymes whose specificity has been determined. There are at least eight distinct types of modifications found on histones (see the legend box on the top left of the figure). Enzyme
s have been identified for acetylation
,
methylation
, demethylation
, phosphorylation
,
ubiquitination, sumoylation,
ADP-ribosylation
,
deimination, and
proline isomerization. For a detailed example of histone modifications in transcription regulation see RNA polymerase control by chromatin structure and table Influence of modifications on gene expression in mammalian cells.
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
into highly condensed chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
makes it inaccessible to the factors required for gene transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
, DNA replication, recombination
Genetic recombination
Genetic recombination is a process by which a molecule of nucleic acid is broken and then joined to a different one. Recombination can occur between similar molecules of DNA, as in homologous recombination, or dissimilar molecules, as in non-homologous end joining. Recombination is a common method...
and repair. Eukaryotes have developed intricate mechanisms to overcome this repressive barrier imposed by the chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
. The nucleosome is composed of an octamer of the four core histone
Histone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
s (H3, H4, H2A, H2B) around which 147 base pairs of DNA are wrapped. Several distinct classes of enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
can modify histone
Histone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
s at multiple sites. The figure on the right enlists those histone-modifying enzymes whose specificity has been determined. There are at least eight distinct types of modifications found on histones (see the legend box on the top left of the figure). Enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s have been identified for acetylation
Acetylation
Acetylation describes a reaction that introduces an acetyl functional group into a chemical compound...
,
methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
, demethylation
Demethylation
Demethylation is the chemical process resulting in the removal a of methyl group from a molecule.A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen atoms....
, phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
,
ubiquitination, sumoylation,
ADP-ribosylation
ADP-ribosylation
ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein. These reactions are involved in cell signaling and the control of many cell processes, including DNA repair and apoptosis.-ADP-ribosylation enzymes:...
,
deimination, and
proline isomerization. For a detailed example of histone modifications in transcription regulation see RNA polymerase control by chromatin structure and table Influence of modifications on gene expression in mammalian cells.
See also
- Histone deacetylaseHistone deacetylaseHistone deacetylases are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. Its action is opposite to that of histone...
s - Histone methyltransferaseHistone methyltransferaseHistone methyltransferases are enzymes, histone-lysine N-methyltransferase and histone-arginine N-methyltransferase, that catalyze the transfer of one to three methyl groups from the cofactor S-Adenosyl methionine to lysine and arginine residues of histone proteins...
- Histone acetyltransferaseHistone acetyltransferaseHistone acetyltransferases are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl CoA to form ε-N-acetyl lysine....
See also
- NucleosomeNucleosomeNucleosomes are the basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound around a histone protein core. This structure is often compared to thread wrapped around a spool....
- ChromatinChromatinChromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
- Histone deacetylaseHistone deacetylaseHistone deacetylases are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. Its action is opposite to that of histone...
- Histone acetyltransferaseHistone acetyltransferaseHistone acetyltransferases are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl CoA to form ε-N-acetyl lysine....
- Histone methyltransferaseHistone methyltransferaseHistone methyltransferases are enzymes, histone-lysine N-methyltransferase and histone-arginine N-methyltransferase, that catalyze the transfer of one to three methyl groups from the cofactor S-Adenosyl methionine to lysine and arginine residues of histone proteins...
- PRMT4 pathwayPRMT4 pathwayProtein arginine N-methyltransferase-4 methylation of arginine residues within proteins plays a critical key role in transcriptional regulation . PRMT4 binds to the classes of transcriptional activators known as p160 and CBP/p300. The modified forms of these proteins are involved in stimulation of...