Reduced histone gene copy number disrupts Drosophila Polycomb function.

Area of Science:

• Cell Biology
• Developmental Biology
• Genetics

Background:

• Animal cell chromatin contains canonical histones for genome packaging during S phase and variant histones with specialized functions throughout the cell cycle.
• Understanding the cooperation between canonical and variant histones is crucial for comprehending chromatin's role in normal and pathological development.

Purpose of the Study:

• To investigate the coordination between canonical histone H3.2 and variant histone H3.3 expression in Drosophila development.
• To identify genes involved in the coordinate regulation of canonical and variant histones.

Main Methods:

• Screened for heterozygous chromosome 3 deficiencies that impair development in flies with reduced H3.2 and H3.3 gene copy number.
• Assessed the impact of Polycomb gene dosage on the viability of animals lacking H3.3.
• Analyzed the effect of Polycomb mutations on the expression of the Polycomb target gene Ubx and the development of ectopic sex combs.

Main Results:

• Variant histone H3.3 is essential for Drosophila development only when canonical histone gene copy number is reduced, indicating a need for coordinated expression.
• Identified two regions on chromosome 3 affecting development in flies with reduced H3.2 and H3.3, including the Polycomb gene region.
• Reduced Polycomb dosage decreased viability in animals lacking H3.3, and Polycomb mutations caused Ubx de-repression and ectopic sex combs when H3 gene copy number was reduced.

Conclusions:

• Coordination between canonical H3.2 and variant H3.3 expression is necessary to provide sufficient H3 protein for normal genome function and development.
• Polycomb-mediated facultative heterochromatin function is compromised when the gene copy number of canonical and variant H3 falls below a critical threshold.