Reduced histone gene copy number disrupts Drosophila Polycomb function

Area of Science:

• Cellular biology
• Developmental biology
• Genetics

Background:

• Chromatin structure relies on canonical histones for genome packaging during S phase.
• Variant histones have specialized roles and are expressed throughout the cell cycle.

Approach:

• Investigated the interplay between canonical histone H3.2 and variant histone H3.3 in *Drosophila* development.
• Screened for chromosome 3 deficiencies affecting flies with reduced H3.2 and H3.3 gene copy number.
• Examined the role of the Polycomb gene in this regulatory network.

Key Points:

• Variant histone H3.3 is crucial for development only when canonical histone gene copy number is reduced.
• Coordination between H3.2 and H3.3 expression ensures sufficient H3 protein for genome function.
• Polycomb gene is identified as a key regulator in this process.

Conclusions:

• Polycomb-mediated facultative heterochromatin function is impaired when canonical and variant H3 gene copy numbers are critically low.
• Reduced Polycomb dosage decreases viability in animals lacking H3.3.
• Heterozygous Polycomb mutations lead to de-repression of Ubx and ectopic sex combs under reduced H3 dosage.