HUANG2 Eukaryotic Transcription Regulation & Epigenetics

What is Position Effect Variegation (PEV)?

PEV is a phenomenon where a gene’s expression is variably silenced depending on its position relative to heterochromatin, resulting in a mosaic pattern of gene expression.

What is the molecular basis of PEV?

The spreading of heterochromatin into euchromatic regions leads to stochastic silencing of adjacent genes.

What are the two types of heterochromatin?

1.Constitutive heterochromatin (permanently silenced regions, e.g., centromeres and telomeres) AND

2.Facultative heterochromatin (can switch between active and inactive states, e.g., X-inactivation).

Which proteins are commonly involved in heterochromatin formation?

HP1 (Heterochromatin Protein 1), SUV39H1 (Histone Methyltransferase), and histone deacetylases.

What histone modification is a hallmark of heterochromatin?

Trimethylation of histone H3 at lysine 9 (H3K9me3).

Why does Position Effect Variegation lead to a mosaic phenotype?

Because the spreading of heterochromatin is variable, some cells will have the gene silenced, while others will express it, resulting in patches of different expression.

What is an example of Position Effect Variegation in Drosophila melanogaster?

The variegated expression of the white gene when it is moved near heterochromatin, leading to red and white patches in the eyes.

What are the 3 factors that influence the extent of PEV?

The distance of the gene from heterochromatin, the strength of boundary elements, and the availability of heterochromatin proteins.

How can the spreading of heterochromatin be limited?

Through boundary elements or insulators that prevent the spread of heterochromatin into active gene regions.

Can heterochromatin patterns be inherited by progeny cells?

Yes, heterochromatin patterns can be inherited through cell divisions. This is mediated by epigenetic marks (such as H3K9me3) and associated proteins, ensuring stable gene silencing in progeny cells.

When does the spread of heterochromatin occur?

Spreading of heterochromatin happens at some point during embryonic development.

How can chromosomal inversions lead to Position Effect Variegation (PEV)?

When a chromosomal inversion relocates a gene that was in a euchromatic region close to or within a heterochromatic region, the spread of heterochromatin can variably silence the relocated gene, causing PEV.

Can the nucleation of heterochromatin be reversed? Through using what?

Yes, nucleation can be reversed through the action of histone demethylases, histone acetyltransferases, and chromatin remodeling complexes, restoring a more open chromatin state.

What does Su(var) stand for in PEV? What happens to them when they are mutated?

Su(var) stands for Suppressor of Variegation. It refers to genes that, when mutated, reduce the extent of heterochromatin spreading, thereby increasing gene expression in variegated regions.

What does E(var) stand for in PEV? What happens to them when they are mutated?

E(var) stands for Enhancer of Variegation. It refers to genes that, when mutated, enhance the spread of heterochromatin, thereby increasing the silencing of genes and reducing expression in variegated regions.

What is the effect of Su(var) mutations on PEV in Drosophila eye color?

Su(var) mutations decrease heterochromatin spreading, leading to more red pigment expression in the eyes (less silencing of the white gene), resulting in a more uniform red eye color.

What is the effect of E(var) mutations on PEV in Drosophila eye color?

E(var) mutations increase heterochromatin spreading, enhancing the silencing of the white gene, leading to more white patches in the eyes, resulting in a more variegated (mottled) appearance.

What are the two main functional domains of the HP1 protein?

HP1 contains two key domains: the Chromodomain (CD) and the Chromoshadow domain (CSD).

What is the function of the HP1 Chromodomain (CD)?

The Chromodomain binds specifically to trimethylated lysine 9 on histone H3 (H3K9me3), which is a hallmark of heterochromatin, allowing HP1 to recognize and bind to heterochromatic regions.

What is the function of the HP1 Chromoshadow Domain (CSD)?

The Chromoshadow domain mediates protein-protein interactions, allowing HP1 to dimerize and interact with other proteins involved in heterochromatin formation, such as histone methyltransferases, chromatin remodelers, and other HP1 molecules.