Srinivas Ramachandran, PhD

​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.