Assistant Professor
Ph.D.,
Chromosome Organization,
Chromatin Structure and Gene Expression
Eukaryotic chromosomes are packaged into chromatin, whose
repeating nucleosomal substructure is composed of DNA
wrapped around histone proteins. Nucleosomes interact with many other proteins to form dynamic, higher-order
structures whose forms and functions are poorly understood. My research is focused on the formidable
challenge of understanding the role of chromatin dynamics and nuclear
organization in essential nuclear processes such as gene expression. My approach integrates the methods of biochemistry,
genetics, and molecular and cell biology to understand the mechanisms of action
of the class of chromosomal elements called chromatin domain insulator elements
(also called boundary elements). I am
also interested in exploring the possibility that insulators can be developed
into useful tools for reducing chromosomal position-effects on transgene expression levels in medical and research
applications.
Insulators
define possible regulatory interactions within genomes. They block enhancer-promoter communication,
but only when located between the enhancer and promoter. They could do this by acting as roadblocks
that stop the propagation of active or repressed chromatin states. To test this model, and to determine if
different insulators are mechanistically similar, I am currently assaying the
ability of various insulators to block the propagation of altered chromatin
states in transgenic flies. This is
being done in collaboration with Dr.
Understanding
how insulators limit communication between enhancers and promoters will address
how enhancers find their target promoters, even when separated by tens of kilobases, without promiscuously interacting with other
promoters. The
role played by insulators in regulating enhancer-promoter interactions suggests
they might play a broader role in the organization of chromosomes into
functionally separate domains. Thus, understanding mechanisms governing
insulator assembly and function should provide insight into the relationship
between higher-order chromatin structure, nuclear organization, and gene
regulation.
Hart, C.M., Cuvier,
O., and
Cuvier, O., Hart, C.M., and
Hart, C.M. and
Hart, C.M., Zhao, K., and
Zhao, K., Hart, C.M., and