Regulation of Chromatin Structure and Gene Expression in Stem Cells

How does chromatin structure impact gene regulation and cell fate?
How is chromatin structure altered during cellular transitions, such as di
fferentiation?

In eukaryotes, relatively large amounts of DNA must be packed into microscopic nuclei within each cell. This is achieved via the formation of highly-organized, yet dynamic chromatin structure in cells. Chromatin affects nuclear processes like gene expression, DNA replication and recombination by several mechanisms, including inhibition of transcription factor binding and localization of genes to transcriptionally active or inactive regions of the nucleus.

Stem cells – cells that are capable of generating any cell type of a tissue or organism – need to remain developmentally flexible in order to be able to self-renew (generate more stem cells) or differentiate into various somatic cell types. To maintain this flexibility, embryonic stem cells maintain a unique chromatin structure that is unusually dynamic and exhibits an atypical pattern of histone modifications at the regulatory sequences of some developmentally regulated genes. In spite of this, the functions of chromatin structure in regulation of stem cell fate remain largely unknown.

We are interested in the mechanisms by which chromatin structure and chromatin regulatory proteins impact gene expression, self-renewal and differentiation in stem cells. To study these processes, we utilize an array of molecular, cellular, genetic, biochemical and systems level approaches. Our long-term goal is to understand how chromatin structure and chromatin regulators help control transcriptional networks that regulate cell fate, and how these networks are rewired during cellular transitions like differentiation.