Determining the cell-specific function of chromatin organization

Eukaryotic genomes are folded into the high-order chromatin structure, which intrinsically regulates all DNA-dependent processes. However, it remains largely unknown how the genome structure is used and modulated in dynamic developmental processes. Chromatin architectural proteins are a class of regulatory factors essential for genome organization.

We have studied a novel evolutionarily conserved protein family, the BEN family. The molecular properties of the BEN proteins conform the general requirement of an architectural protein.

While the known architectural proteins are found in all the cells, the BEN proteins are expressed in specific cell types.

This makes them an excellent model to study how architectural factors guide rapid developmental process through regulating chromatin dynamics.In this project, we aim to reveal novel conserved mechanisms of genome organization.

We will use the BEN proteins as the example to elucidate the functional link between genome organization, gene regulation and cell specification in the developing brain.

In the four years of time frame, we will integrate advanced genomic and biochemical approaches with molecular genetics, and exploit our discovery from Drosophilaas an entry point to characterize candidate mechanisms in mammals. Mutations in chromatin architectural proteins are associated with multiple human diseases.

The new knowledge from this study will provide mechanistic insights into the pathology of these diseases.