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			File:The_basic_unit_of_chromatin_organization_is_the_nucleosome,_which_comprises_147_bp_of_DNA_wrapped_ar.jpg\|The basic unit of chromatin organization is the nucleosome
			File:Basic_units_of_chromatin_structure.svg\|Basic units of chromatin structure
			File:Histone_acetylation_and_deacetylation.jpg\|Histone acetylation and deacetylation
			File:General_structural_formula_of_phosphoryl_group.svg\|General structural formula of phosphoryl group
			File:O-GlcNAc_clear_red.png\|O-GlcNAc
			File:ADP_ribose.svg\|ADP ribose
			File:Citrullination.svg\|Citrullination
			File:Proline-cis-trans-isomerisation.svg\|Proline cis-trans isomerisation
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'''Histone-modifying enzymes''' are a group of enzymes that play a crucial role in the regulation of [[gene expression]] by chemically modifying [[histones]], which are proteins around which [[DNA]] is wound in [[chromatin]]. These modifications can either activate or repress gene expression, making histone-modifying enzymes essential for many biological processes, including [[cell cycle]], [[DNA repair]], and [[development]].

==Types of Histone Modifications==
Histone modifications include methylation, acetylation, phosphorylation, ubiquitination, and sumoylation, among others. The most studied modifications are histone acetylation and methylation.

===Histone Acetylation===
Histone acetylation is typically associated with gene activation. It is carried out by enzymes known as [[histone acetyltransferases (HATs)]] which add acetyl groups to lysine residues on histones, reducing their positive charge and decreasing the interaction between histones and DNA. This change allows for a more relaxed chromatin structure, facilitating access for transcription factors and other proteins necessary for gene expression. Conversely, [[histone deacetylases (HDACs)]] remove acetyl groups, leading to a more condensed chromatin structure and gene repression.

===Histone Methylation===
Histone methylation can either activate or repress gene expression, depending on the specific lysine or arginine residue that is methylated. [[Histone methyltransferases (HMTs)]] add methyl groups to histones, while [[histone demethylases (HDMs)]] remove them. The effect of histone methylation on gene expression is determined by the number of methyl groups added and the specific amino acid residues that are modified.

==Function and Mechanism==
Histone-modifying enzymes regulate gene expression by altering the chromatin structure, making it either more accessible or less accessible to the transcription machinery. These modifications serve as signals for other proteins that either promote or inhibit transcription. For example, acetylated histones are often recognized by proteins with bromodomains, which are associated with gene activation. In contrast, methylated histones can be recognized by proteins with chromodomains, which can lead to either gene activation or repression, depending on the context.

==Clinical Significance==
Aberrant activity of histone-modifying enzymes has been linked to various diseases, including [[cancer]], [[neurodegenerative diseases]], and [[developmental disorders]]. For instance, mutations in genes encoding these enzymes or changes in their activity can lead to inappropriate gene expression, contributing to the development and progression of cancer. As a result, histone-modifying enzymes have become targets for therapeutic intervention. Drugs that inhibit HDACs, for example, are being used in the treatment of certain types of cancer.

==Research and Future Directions==
Research in the field of histone modifications and their regulatory enzymes continues to uncover the complex network of gene regulation. Understanding the specific roles of these enzymes in different biological contexts and diseases may lead to the development of more targeted therapies with fewer side effects.

[[Category:Biochemistry]]
[[Category:Genetics]]
[[Category:Molecular biology]]
[[Category:Epigenetics]]

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Histone-modifying enzymes - Revision history

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