Kristin C. Scott, PhD
Research Track Faculty
Assistant Research Professor
376 CARL Building
Box 3053 DUMC
Durham, NC 27710
Phone: (919) 684-7938
Fax: (919) 668-0795
We are engaged in projects exploring the packaging of DNA into various types of chromatin, and the epigenetic effects of alternative chromatin packaging on centromere function, genome stability and gene expression. We explore these basic biological questions using experimental approaches in the versatile model organism fission yeast,Schizosaccharomyces pombe, integrating genetics, molecular biology, cytology and genomics.
Regulation of centromere structure and function
The structure of chromatin in the genome is not uniform. Single-copy and low-copy number genes that give rise to most cellular mRNAs are packaged in euchromatin. In contrast, the heterochromatic fraction of the genome corresponds to highly condensed chromosomal regions, from which few mRNAs are produced. Some heterochromatic states are capable of “oozing” in cis across genomic DNA, thus silencing nearby genes. This creates a unique challenge for the cell: how to regulate heterochromatin assembly to ensure that appropriate genes are turned off, while protecting the expression of other genes.
Our previous work identified a distinct chromatin barrier element, including a pair of tRNA genes, present at the border between pericentromeric heterochromatin and the specialized, CENP-A containing core chromatin at the fission yeast centromere. The tRNA gene is expressed, despite its position adjacent to pericentromeric heterochromatin. Moreover, interruption of the barrier by insertion of exogenous DNA sequences can lead to a variety of abnormal chromosome phenotypes, including defects in cell growth and chromosome mis-segregation. These initial studies have led us to investigate the mechanisms of centromeric barrier activity, as well as elucidate the putative roles of chromatin barriers in chromosome architecture and genome stability through mitosis and meiosis.
Epigenetic inheritance of chromatin states
Along with genomic signals encoded in the DNA, such as chromatin barriers, epigenetic modifications to both chromatin and DNA regulate the function of the genome. Despite a detailed understanding of the histone and DNA modification patterns associated with the epigenetic regulation of the genome, the mechanism of epigenetic inheritance, or how a chromatin environment is stably propagated through numerous cell divisions, is only beginning to be explored. We recently developed a heterochromatin inheritance assay to elucidate the genetic, molecular and cellular pathways that control the inheritance of de novo heterochromatin domains. Because the fission yeast lacks DNA methylation, the dominant epigenetic mark in higher eukaryotes that is faithfully conserved following replication, the inheritance assay has great potential for identifying alternative, and/or complementary epigenetic pathways that may function in all eukaryotes.