How does histone modification affect gene expression?

Histone modification affects gene expression by altering the structure of chromatin, thereby influencing gene accessibility to transcription machinery.

Histones are proteins that DNA wraps around, forming a complex called chromatin. This structure not only helps to compact DNA into the nucleus but also plays a crucial role in gene regulation. The modification of histones, such as methylation, acetylation, phosphorylation, and ubiquitination, can change the structure of the chromatin, thereby influencing the accessibility of genes to the transcription machinery and ultimately affecting gene expression.

Acetylation, for instance, typically loosens the chromatin structure. This is because the addition of an acetyl group to a histone neutralises its positive charge, reducing the affinity between the histone and the negatively charged DNA. As a result, the DNA becomes less tightly bound to the histone, making it more accessible to transcription factors and RNA polymerase, the enzyme that synthesises RNA from a DNA template. This generally leads to an increase in gene expression.

On the other hand, methylation of histones can either activate or repress gene expression, depending on the specific context. For example, methylation of histone H3 at lysine 4 (H3K4) is often associated with gene activation, while methylation at lysine 9 (H3K9) or 27 (H3K27) is typically linked to gene repression. This is because different methylation patterns can recruit different proteins that either promote or inhibit the transcription process.

Phosphorylation and ubiquitination are other types of histone modifications that can also influence gene expression. Phosphorylation often occurs in response to cellular signals and can lead to changes in chromatin structure that facilitate gene expression. Ubiquitination, meanwhile, can affect gene expression by altering the stability of histones or by recruiting proteins involved in transcription.

In summary, histone modifications can profoundly influence gene expression by changing the structure of chromatin and thereby controlling the accessibility of genes to the transcription machinery. These modifications are part of a complex regulatory system that allows cells to respond to changes in their environment and to regulate their growth and development.