Professor and Chair
parthun.1@osu.edu
614-292-6215
Research Interests
My laboratory studies the role of histone post-translational modifications in the assembly and regulation of chromatin structure.
We have a variety of projects that are related to the analysis of our mouse knockout of the enzyme histone acetyltransferase 1 (Hat1). This enzyme is responsible for the acetylation of histone H4 during the process of chromatin assembly. Loss of this enzyme results in a number of interesting phenotypes, such as developmental defects of the lung, craniofacial defects, liver defects and genome instability. Projects are available that focus on any of these aspects of Hat1 function.
The DNA of eukaryotic cells is packaged in a nucleoprotein complex known as chromatin. The fundamental unit of chromatin is the nucleosome, which consists of approximately two turns of DNA wrapped around a protein core of histones H2A, H2B, H3 and H4. The core histones are important not only for the structural packaging of DNA in the nucleus but also for regulating many cellular processes that use DNA as a substrate. The proper control of these processes, which include transcription, replication, recombination and DNA repair, is essential for maintaining cellular growth control.
Much of the regulatory potential of the histones lies in their NH2-termini. The NH2-terminal tails, the first ~30 amino acids of each histone, are largely unstructured and contain high concentrations of lysine and arginine residues. These domains appear to project out from the nucleosome structure and, as such, are in a position to make contacts with both the DNA as it wraps around the histone octamer and with chromatin associated proteins. An intriguing characteristic of the NH2-terminal tails is that their physical properties are regulated by extensive post-translational modifications, which include phosphorylation, methylation, ubiquitination, ADP-ribosylation, and acetylation.
Acetylation of core histone NH2-terminal tails was discovered more than 30 years ago and has been the most extensively studied histone modification. Histone acetylation occurs on lysine residues, neutralizing their positive charge and changing their structure. As such, this modification is likely to affect the interaction of histones with both DNA and other proteins. The acetylation of the core histones is a dynamic process, with the acetylation state of a given histone determined by the actions of enzymes that add acetyl groups (histone acetyltransferases) and enzymes that remove them (histone deacetylases).
Our laboratory is focused on the type B histone acetyltransferases. This class of enzymes is localized to the cytoplasm and specifically acetylates free histones. These enzymes are thought to acetylate newly synthesized histones during the process of chromatin assembly. Using both biochemical and genetic methods we are currently characterizing the in vivo role of this intriguing, evolutionarily conserved, enzyme family.
Education and Training
Ph.D. - Indiana University
Post Doctoral - Northwestern University, Fred Hutchinson Cancer Research Center
Location
Office: 206G Rightmire Hall
Lab: 220 Rightmire Hall