Single chromatin fiber profiling and nucleosome position mapping in the human brain
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.
Authors
- Cyril Peter (ORCID: https://orcid.org/0000-0001-9190-8724)
- Mitchell R. Vollger (ORCID: https://orcid.org/0000-0002-8651-1615)
- Tova Y. Lambert (ORCID: https://orcid.org/0000-0002-5005-0087)
- Bibi Kassim
- Schahram Akbarian (ORCID: https://orcid.org/0000-0001-7700-0891)
- Kiran Kumar Girdhar (ORCID: https://orcid.org/0000-0002-5622-042X)
- Nadejda M. Tsankova (ORCID: https://orcid.org/0000-0002-5333-312X)
- Xuedi Wang (ORCID: https://orcid.org/0009-0002-0709-8349)
- Viviana D. Evans (ORCID: https://orcid.org/0000-0001-8824-3274)
- Maya Fridrikh
- Aman Agarwal (ORCID: https://orcid.org/0009-0005-5813-7047)
- Andrew B. Stergachis (ORCID: https://orcid.org/0000-0002-1299-3674)
- Sathiji Nageshwaran (ORCID: https://orcid.org/0000-0003-3931-2573)
- Panos Roussos (ORCID: https://orcid.org/0000-0002-4640-6239)
- Robert Sebra (ORCID: https://orcid.org/0000-0001-9267-2426)
- Travis Dawson (ORCID: https://orcid.org/0000-0002-9609-793X)
- Risa Watanabe (ORCID: https://orcid.org/0000-0002-0186-9029)
- Behnam Javidfar (ORCID: https://orcid.org/0000-0003-2754-2742)
- Dan Hasson (ORCID: https://orcid.org/0000-0001-7943-1636)
Institutions
- Allen Institute for Brain Science (US)
- University of Washington Medical Center (US)
- Brotman Baty Institute (US)
- New York Genome Center (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Cell Reports Methods
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1016/j.crmeth.2024.100911
- Citations
- 4
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- Foundation for the National Institutes of Health
- Georgia Clinical and Translational Science Alliance
- National Institutes of Health
- National Institute of Mental Health
- National Institute on Drug Abuse
- National Center for Advancing Translational Sciences