Faculty Research Interest

Single-Molecule Manipulation Studies of Chromatin Dynamics, Chromatin Remodeling, and Protein Folding

Faculty Record

In eukaryotes, most regions of genomic DNA are sequestered from specific-binding proteins because of their hierarchical packaging into chromatin. How proteins like transcription factors access genomic DNA and find their target sequences remains an unsolved fundamental problem. The last decade has seen rapid progress toward an understanding of how eukaryotic cells overcome this obstacle. A key element of the puzzle is the discovery of an “index” system that marks different functional domains of chromatin. The indexing of chromatin structure is mediated by covalent histone modifications through a variety of posttranscriptional mechanisms such as acetylation, methylation, and phosphorylation, of histone-tail domains. These modifications are tantamount to a “histone-code” that can be read specifically by a set of multi-subunit chromatin remodeling factors (remodelers) that use the energy of ATP hydrolysis to locally alter chromatin structure and expose genomic DNA.

My laboratory is interested in single-molecule approaches and their applications in chromatin biology. Specifically, we now focus upon the following areas:

(1) Development of high-resolution optical tweezer instruments for single-molecule studies.
(2) The structure and dynamics of chromatin in the absence and presence of histone modifications.
(3) How the chromatin structure and dynamics is altered by the remodelers, i.e., the molecular mechanisms of ATP-dependent chromatin remodeling.
(4) How the chromatin remodeling activity is modulated by the histone modifications.

We are also curious about how protein folding is coupled to force generation in certain important biological processes.