Presenter: Collin Hickmann
Faculty Mentor: Tereza Ormsby, Eric Selker
Presentation Type: Oral
Primary Research Area: Science
Major: Biochemistry
Funding Source: Presidential Undergraduate Research Scholars Program (PURS), Undergraduate Research Opportunity Program (UROP), $5,000; Oregon Undergraduate Researchers in SPUR (OURS), National Institute of Child Health and Human Development (NICHD), $5,000
Heterochromatin is a minimally transcribed, densely bundled complex of DNA and associated factors comprising large regions of the eukaryotic genome. It is essential for chromosome stability, genome integrity, gene regulation, and the silencing of transposons. The filamentous fungus Neurospora crassa is often employed as a model organism to study the epigenetic regulation of heterochromatin. In Neurospora, the conserved scaffolding protein heterochromatin protein 1 (HP1) binds H3 histones marked by lysine nine trimethylation (H3K9me3) and recruits other proteins to form at least three distinct complexes. HP1 recruits the DIM-2 DNA methyltransferase, which catalyzes DNA methylation. HP1 is also an essential component of both the HCHC histone deacetylation complex, which facilitates centromeric silencing, and the DMM complex, which limits aberrant heterochromatin spreading. However, it’s unclear how these disparate functions are coordinated. We hypothesized that they are modulated by post-translational modifications (PTMs) of HP1. Previously, we used mass spectrometry to identify HP1 sites harboring methylation, acetylation, formylation, and phosphorylation. I used amino acid substitutions at a subset of these sites to prevent individual PTMs in vivo. Substitutions at multiple sites were found to cause a substantial decrease in centromeric silencing independent of DNA methylation. These results suggest that the recruitment of HCHC to incipient heterochromatin may be selectively mediated by specific PTMs.