Nucleosome dynamics during chromatin remodeling in vivo.

For transcription factor binding and for transcription to take place, nucleosomes would have to be disrupted and reformed at active regions of the genome. However, little is known about how the nucleosome structure is altered during these processes. We constructed a molecular model for H4-S47C-anchored chemical cleavage mapping, which was originally developed to determine nucleosome positions genome-wide at base-pair resolution. Applying our molecular model to genome-wide H4-S47C-anchored chemical cleavage data, we identified nucleosomes with asymmetric histone-DNA contacts that were highly enriched at positions proximal to promoters.

Using a combination of H4S47C-anchored cleavage mapping, MNase cleavage mapping, and ChIP-seq, we determined that the asymmetric loss of histone-DNA contacts was due to the formation of a nucleosome-remodeler complex that featured partial unwrapping and protection of nucleosomal DNA during chromatin remodeling. This study demonstrated the ability to map alternate nucleosome structures formed during active processes in vivo.

1. Ramachandran, S., Zentner G. E., Henikoff, S. “Asymmetric nucleosomes flank promoters in the budding yeast genome”, Genome Research, 25(3):381-90 (2015) pubmed     journal
2. Ramachandran S., and Henikoff, S. “Nucleosome dynamics during chromatin remodeling in vivo”, Nucleus 7(1):20-6 (2016)  pubmed    journal