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7.8: Histone Modification

JoVE Core
Cell Biology

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Histone Modification

7.8: Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.


The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase, removes the acetyl group from acetylated histones. The lysine amino acids at position 4 and 9 of N-terminal histone tail are often acetylated and deacetylated. Acetylation increases the negative charge of histones. This weakens the DNA-histone interaction resulting in loosening of chromatin and increased access to DNA. For example, in the erythroid cells, beta-globin gene is associated with acetylated histones that increase its expression. In non-erythroid cells where the gene is inactive, it is found to be associated with nonacetylated histones.


The histone tails at the lysine 9 position of histone H3 can be di- or tri-methylated by enzyme histone methyltransferase. This methylation can initiate the binding of nonhistone proteins and increase chromatin compaction. Methylation increases the positive charge on the histones, resulting in increased affinity between negatively charged DNA and histones and higher chromatin compaction. Repressed chromatin, also known as heterochromatin, is highly methylated.

Summary table of histone modifications and their effect on gene expression

Histone modification Effect on gene expression
Acetylated lysine Activation
Hypoacetylated lysine Repression
Phosphorylated serine/threonine Activation
Methylated arginine Activation
Methylated lysine Repression
Ubiquitinylated lysine Activation/Repression

The histone codes or modifications are epigenetically inherited, meaning these modifications are not genetically coded. Hence, these modifications are faithfully passed on to the next cell during each cell division as an epigenetic memory.

Suggested Reading


Histone Modification Epigenetics Chromatin DNA Packaging Post-translational Modifications Acetylation Methylation Phosphorylation Histone Code Gene Expression Regulation

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