538C Poster - 07. Chromatin, epigenetics and genomics
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Jeanne-Marie McPherson; Robert Duronio; Daniel McKay

Affiliation: University of North Carolina at Chapel Hill

Keywords:
d. histone variants and modifications; j. epigenetics

Histones are essential for packaging and organizing DNA into chromatin, which regulates all DNA-dependent processes. Regulation of histone abundance is critical, as too many or too few histones is toxic to cells and disrupts development. Cells contain two types of histones: canonical histones expressed during S phase of the cell cycle and variant histones expressed throughout the cell cycle and in post-mitotic cells. Canonical histone H3.2 and variant histone H3.3 are highly conserved across eukaryotes, making Drosophila melanogaster an ideal model to study histone biology. By manipulating canonical H3.2 copy number in Drosophila we discovered that H3.3 is essential for development when canonical histone gene copy number is reduced, uncovering a previously unknown requirement for coordination between canonical H3.2 and variant H3.3 expression. We hypothesize that cells possess a homeostatic mechanism to maintain the correct relative expression of canonical H3.2 and variant H3.3. Histone homeostatic mechanisms could affect histone expression at many levels, including transcription, translation, deposition, or protein turnover. Thus far we have discovered that reducing canonical H3.2 copy number does not result in increased variant H3.3 transcript or protein levels. We will explore the mechanisms of histone homeostasis by conducting a forward genetic screen to identify factors involved in canonical and variant histone coordination. This project expands our fundamental understanding of how canonical and variant histones cooperate to regulate genome function.