In (or out) of the loop: Understanding Chromatin Organization and Gene Expression in Vertebrate Development

Title: In (or out) of the Loop: Understanding Chromatin Organization and Gene Expression in Vertebrate Development.

Abstract: For eukaryotic organisms (cells that have organelles such as a nucleus) storage of their genomic information poses two problems: One, the genome has to fit in the nucleus and two, while packaged in the nucleus the genome must still be accessible for gene expression (producing RNA to make protein) and activating replication (copying the genome for cell division). General mechanisms for how genomes are stored reveal that protein interacts with DNA (a general complex called chromatin) to pack the genome into smaller structures to fit into the nucleus.  It has also been shown that active genes tend to be less packed (referred to as open chromatin) while inactive genes are more densely packed (closed chromatin).  Furthermore, recent genome wide studies have indicated that chromatin is looped and that the points where chromatin contacts are created, there are important sequences that regulate gene activity.

Our research focuses on understand how these loops are created a maintained during vertebrate development.  Using the model organism Danio rerio (zebrafish) we aim at understanding the molecular basis of loop dynamics in a cluster of developmentally essential genes encoding HOX proteins. Hox genes are essential for metazoan hindbrain development and have been shown to play a role in cancer. Hox genes have also been shown to be regulated by changes in chromatin organization.  Still, little is known about how the specific factors that regulate Hox expression interact with the general machinery that regulates chromatin organization, or how this works within the context of embryogenesis. Understanding how the chromatin structures that regulate Hox gene expression are regulated have the further potential to identify new therapeutic targets to fight HOX related disease.