Examples of histone modifications are acetylation (by histone acetyltransferase, or HAT), which is often linked to gene activation, and deacetylation (by histone deacetylases, or HDACs), which often leads to gene silencing typical of heterochromatin. Such heterochromatinization is initiated from a nucleation site and spreads bidirectionally until encountering boundaries that delimit the silenced areas. Recall from earlier in the text (see Chapter 4) the brief discussion of position effect, where repositioning of the w⁺ allele in Drosophila by translocation or inversion near heterochromatin produces intermittent w⁺ activity. In the heterozygous state (w⁺/w) a variegated eye is produced, with white and red patches. How might one explain position-effect variegation in terms of histone acetylation and/or deacetylation?

Key Concepts

Histone Modifications

Histone modifications, such as acetylation and deacetylation, are chemical changes to histone proteins that influence gene expression. Acetylation, typically facilitated by histone acetyltransferases (HATs), is associated with gene activation by loosening DNA-histone interactions, allowing transcription factors access to DNA. Conversely, deacetylation, carried out by histone deacetylases (HDACs), leads to tighter DNA packaging and gene silencing, often resulting in heterochromatin formation.

Heterochromatin and Gene Silencing

Heterochromatin is a tightly packed form of DNA that is generally transcriptionally inactive, meaning genes located within it are often silenced. This silencing is crucial for maintaining genomic stability and regulating gene expression. The formation of heterochromatin can be influenced by histone modifications, particularly through deacetylation, which promotes a more compact chromatin structure, thereby inhibiting transcription.

Position Effect Variegation

Position effect variegation (PEV) occurs when the expression of a gene is influenced by its chromosomal location, particularly when it is relocated near heterochromatin. In Drosophila, the w⁺ allele can exhibit variable expression levels, resulting in a mosaic pattern of red and white eye color. This phenomenon can be explained by the differential histone acetylation and deacetylation at the gene's new location, leading to inconsistent access to transcription machinery and variable gene activity.