Recruitment of chromatin remodeling complexes to genomic loci by Rsc3, Rsc30, and other site-specific DNA-binding transcription factors in yeast. Whole genome localization of chromatin remodeling complexes
Whole genome localization of chromatin remodelers and transcription complexes. Association of the RSC complex with RNA polymerase III. Microarray applications
Genetic and biochemical characterization of nuclear aminooxidase enzymes in Schizosaccharomyces pombe.
I am interested in the biochemistry of putative histone lysine demethylases in S. pombe, and of any possible proteins and other factors that modulate their activity to affect chromatin structure and gene regulation.
We are exploring structure/function relationships within Sth1, the catalytic subunit of RSC, and between it and other members of the remodeling complex. The domain structure of Sth1 consists of a centrally located ATPase/translocase domain required for enzymatic activity, a flanking HSA domain required for interaction with other RSC members, and a C-terminal bromodomain of unknown function. We are overexpressing and purifying fragments of Sth1 alone or in combination with other members of RSC at a scale suitable for crystallographic studies in collaboration with Devin Close and Chris Hill in the Biochemistry Department. Results from the structural studies will be used to design reagents to study Sth1 biochemically and in vivo.
My work in the lab focuses on understanding the function of histone H2A variant, Htz1, in transcription regulation. I would like to understand the dynamics of Htz1 in response to environmental signals, mechanisms of Htz1deposition, and the coordination of Htz1 with other chromatin factors.
Elucidation of the mechanism of leukemogenisis by MLL-fusion proteins (YEATS domain proteins) via the study of their yeast homologs.
My work explores how signaling pathways regulate transcription through chromatin remodeling and other important regulators in Saccharomyces cerevisiae. First, a functional analysis of two subunits in the chromatin remodeling complex RSC, Rsc7 and Rsc14, has provided evidence for a fungal-specific RSC module that has connections to a broad range of signaling pathways. Future studies are examining possible modular functions (recruitment/regulation of RSC) in response to varying signals. Second, my work is examining how RNA polymerase III transcription is regulated in response to diverse cellular signaling programs. Unlike RNA Polymerase II transcription which depends upon multiple co-regulators, RNA polymerase III transcription is regulated by a central factor, the conserved Maf1 protein. Future studies are aimed at discovering mechanistically how Maf1 integrates signals from multiple signaling pathways to repress RNA polymerase III transcription.
Primarily understanding how chromatin structure is remodeled to regulate gene expression. I am interested in characterizing the mechanism underlying nucleosome mobilization by ATP-dependent remodeling complex RSC.
Graduate Student, Department of Oncological Sciences, University of Utah
Nuclear actin and actin-related proteins (ARPs) are essential components of chromatin remodeling complexes and histone acetyltransferase complexes, which together regulate chromatin structure for essential nuclear processes such as nucleosome assembly, DNA replication, DNA repair, and transcription. The yeast SWI/SNF and RSC complexes contain Arp7 and Arp9, and are shown to form a stable heterodimer with the properties of a functional module. Although highly conserved and essential, little is known about the function of nuclear Arps and actin within these complexes. We utilize both genetic and biochemical techniques to elucidate nuclear Arp/actin function.
I am a pediatric physician-scientist with a research background in immunology. My current projects use fission yeast as a model eukaryote to study fundamental and critical processes like transcriptional regulation and the preservation of genomic integrity. Specifically, I study how the recently described phenomena of RNA Interference (RNAi) effects changes to the chemical composition and structure of chromatin, and the biologic repercussions of these changes. I use a wide range of molecular techniques, utilizing the genetic, biochemical, and genomic advantages of our model system.
I work on a novel nuclear amine-oxidase-containing complex in S. pombe with putative histone demethylase activity. We are using genomic, genetic, and biochemical approaches to understand how this complex regulates gene expression.
I study the transcriptome of the fission yeast, S.pombe. To do this, I have developed a microarray technique utilizing an antibody that recognizes RNA-DNA hybrids. Through analysis of this transcriptome, I am especially interested in identifying novel non-coding RNAs and their functions. In my spare time I enjoy skiing, climbing, reading, and long walks through the woods at sunset.
Howard Hughes Medical Institute
Andrew graduated with a BS in Biology from Boise State University in 2005 and entered the Molecular Biology Program at the University of Utah the same year. His research focuses on regulation of RNA Polymerase III by the repressor Maf1in budding yeast. Outside of the lab, Andrew enjoys playing with his daughter and doing genealogy.
|Itrat (Jafri) Harrold, PhD|