Chromatin Structure and Gene Transcription

Coordinate spatial and temporal regulation of gene expression is essential for normal development. If genes are not expressed correctly, the function of a cell will be altered. This may result in excess cell division leading to cancerous tumors, no cell growth resulting in cell loss, or premature differentiation resulting in non-functioning cells. Misregulation of gene expression is a major cause of human disease including cancer and neurodegenerative disorders.

Gene expression is regulated in part by the interactions of genomic DNA with the packaging histone proteins. Research in the Pile laboratory is directed toward understanding how genome packaging affects gene expression. Histones undergo a variety of modifications including acetylation, phosphorylation and methylation, which in turn affect the level of packaging. We are currently investigating how the SIN3 histone modifying complex functions to affect transcription at the epigenetic level. SIN3 is required for viability of multi-cellular organisms and mutations in components in the complex have been linked to defects in cell cycle progression.

Current objectives of the lab are to understand regulatory pathways that affect SIN3 expression and activity and to understand the consequences of SIN3 recruitment at target genes. We are taking a multi-pronged approach to address these questions in the model organism Drosophila melanogaster and human cancer samples. We are utilizing a combination of biochemical, molecular and genetic techniques to understand the mechanism of SIN3 gene regulation. Data from these studies will help to elucidate the contribution of histone modification to signaling cascades that impact cellular decisions critical for proliferation, development and viability.

Lab alumni have gone on to various positions in scientific fields including research in industry, teaching at community colleges, post-doctoral fellowships and attending medical school. Please contact us if you are interested in learning more about our research projects.