In vivo Nucleosome
Structure and Dynamics
Our genomes are packaged in the
nucleus by formation of protein-DNA complexes called nucleosomes. Nucleosomes
regulate access to the genome and must be constantly disrupted and reformed to
shape the accessible DNA landscape. Nucleosomes form due to multiple strong
contacts between the histone octamer (the protein component) and 147 bp of DNA.
Our lab seeks to understand how these contacts break and reform during critical
processes like transcription and replication inside cells. We develop
biochemical methods with genomic readout to infer structural states of
nucleosomes at high spatial and temporal resolution inside cells. We use these
methods to understand how DNA-binding proteins and chromatin remodelers modify
nucleosome structure to modulate DNA accessibility.
Another aspect of the nucleosome
landscape that we are interested in is how chromatin states are remembered:
many chromatin states persist through dilution during replication and
disruption during transcription. How is this cellular memory maintained? By
developing experimental methods that track chromatin states temporally, we aim
to uncover fundamental mechanisms that maintain cellular memory of chromatin
states through successive cell divisions.