Single chromatin fiber profiling and nucleosome position mapping in the human brain.
Publication/Presentation Date
12-16-2024
Abstract
We apply a single-molecule chromatin fiber sequencing (Fiber-seq) protocol designed for amplification-free cell-type-specific mapping of the regulatory architecture at nucleosome resolution along extended ∼10-kb chromatin fibers to neuronal and non-neuronal nuclei sorted from human brain tissue. Specifically, application of this method enables the resolution of cell-selective promoter and enhancer architectures on single fibers, including transcription factor footprinting and position mapping, with sequence-specific fixation of nucleosome arrays flanking transcription start sites and regulatory motifs. We uncover haplotype-specific chromatin patterns, multiple regulatory elements cis-aligned on individual fibers, and accessible chromatin at 20,000 unique sites encompassing retrotransposons and other repeat sequences hitherto "unmappable" by short-read epigenomic sequencing. Overall, we show that Fiber-seq is applicable to human brain tissue, offering sharp demarcation of nucleosome-depleted regions at sites of open chromatin in conjunction with multi-kilobase nucleosomal positioning at single-fiber resolution on a genome-wide scale.
Volume
4
Issue
12
First Page
100911
Last Page
100911
ISSN
2667-2375
Published In/Presented At
Peter, C. J., Agarwal, A., Watanabe, R., Kassim, B. S., Wang, X., Lambert, T. Y., Javidfar, B., Evans, V., Dawson, T., Fridrikh, M., Girdhar, K., Roussos, P., Nageshwaran, S. K., Tsankova, N. M., Sebra, R. P., Vollger, M. R., Stergachis, A. B., Hasson, D., & Akbarian, S. (2024). Single chromatin fiber profiling and nucleosome position mapping in the human brain. Cell reports methods, 4(12), 100911. https://doi.org/10.1016/j.crmeth.2024.100911
Disciplines
Medicine and Health Sciences
PubMedID
39631398
Department(s)
Medical Education
Document Type
Article