Jun 14th, 2019: Our latest paper of identifying nucleosome occupancy and chromatin accessibility on single DNA molecule is selected as the cover of the August Issue of Genome Research.
Single-molecule long-read sequencing reveals the chromatin basis of gene expression.
Wang, Y., Wang, A., Liu, Z.
, Thurman, A., Powers, L.S., Zou, M., Hefel, A., Li, Y., Zabner, J., Au, K.F. Genome Res. Cover photo of issue August 2019
|Combining methyltransferase treatment with nanopore sequencing, Wang et al. developed a new experimental approach “MeSMLR-seq” to map nucleosome occupancy and chromatin accessibility at single long DNA molecules. MeSMLR-seq shows consistent bulk-cell results with existing methods (e.g. MNase-seq and ATAC-seq), but more importantly it brings unprecedented power to capture the single-molecule epigenome. Thus, epigenome heterogeneity can be clearly resolved and subtle but meaningful epigenome differences at single molecules can be discovered. For instance, the MeSMLR-seq data provided the quantitative evidence for the correlation between promoter accessibility and transcription activity. The MeSMLR-seq long reads phased >300 nucleosomes and identified chromatin accessibility of up to 40 adjacent genes simultaneously at single molecules - e.g. the MeSMLR-seq data revealed the coupled chromatin status changes of the adjacent glucose transporter genes responding to the glucose concentration changes. It shows potential to study the association of multiple layers of epigenomes, including base modifications at the same molecules.