Download Dr. Chris Eskiw Dept. of Food and Bioproduct Sciences University of Saskatchewan

COLLOQUIUM TALK
Tuesday, March 8, 2016
12:00 NOON – 1:00 PM
IB 260
Dr. Chris Eskiw
Dept. of Food and Bioproduct Sciences
University of Saskatchewan
Transcription as a driver of genome organization:
The relationship between structure and function
The completion of the Human Genome Project was expected to answer many of the questions regarding
what we are and how we function at the molecular level. Although this project did provide very useful and
insightful information, the primary sequence of our genome is just the first level regulating function (gene
expression). Numerous examples demonstrate that genome folding (organization in 3D space) plays a key role in
gene regulation. What genome folding patterns give rise to the expression of specific genes and how is this folding
mediated? One hypothesis states that transcription is the main driver of how genomes are organized within cells.
Transcription sites are organized into foci and are far fewer in number than the number of genes actively
transcribing. This indicates that genes must share these sites. Ultrastructural imaging using energy filtering
transmission electron microscopy (EFTEM) demonstrated that these foci, called transcription factories, are large
proteinaceous structures measuring many megadaltons in size and have the capacity to contain many polymerizing
complexes and accessory molecules, including transcription factors and splicing machinery. Genes sharing
common regulatory mechanisms are ‘pulled’ together at specific transcription factories due to a sharing of limited
transcriptional resources (such as transcription factors), thus driving genome organization. Changes in growth
conditions or disease states can result in changes in genome organization even at the gross level of chromosome
territory reorganization. We observed that treatment of normal dermal fibroblasts with the antiaging drug
rapamycin drives chromosomes to reorganize which was coincident with a switch in transcriptional program
favoring STAT5A/B-mediated cytokine synthesis. The next question is to determine which specific interactions,
such as gene/gene or gene enhancer, are being driven together by transcription at STAT5A/B transcription
factories in normal healthy cells.