Roadblocks

A DNA motor protein frequently encounters DNA binding proteins and complexes that can interfere, stall, or collapse essential processes. How these roadblocks are resolved or overcome can depend on multiple factors, including their location, the binding strength of interactions, and how they are removed/relocated.

High resolution histone-DNA interaction map We applied the unzipping technique to generate a high resolution map of the strengths of histone-DNA interactions in a nucleosome (Hall et al., NSMB, 2009). These interactions represent a fundamental level of gene regulation through which nucleosome stability, DNA accessibility, transcription, and chromatin higher order structures are controlled.

Passive Nucleosome Transfer Nucleosomes may be passively transferred to a new location, and the transfer is mediated via the formation of a DNA loop and is essentially 100% efficient (Brennan et al, Nature Communications, 2016). These findings suggest a mechanism for the maintenance of the epigenetic landscape during replication where parental nucleosomes may be passively transferred to daughter strands via DNA loop formation. This work highlights the importance of DNA mechanics in fundamental biological processes.

Active Nucleosome Transfer Nucleosomes may also be actively relocated by nucleosome remodelers and in vivo, transcription regulation critically relies on the dynamic competition of nucleosomes and transcription factors. Building upon previous work (Shundrovsky et al., NSMB, 2006), we determined differential roles of the two families of remodelers near promotors: ISWI remodelers may use a bound TF as a reference point to space nucleosomes in the gene body, while SWI/SNF remodelers may utilize a nucleosome to remove a bound TF from the promoter region (Li et al, eLIFE, 2015).