Single-molecule regulatory architectures captured by chromatin fiber sequencing
Abstract
Primary architecture of chromatin fibers: The organization of chromosomal DNA, including the positioning of nucleosomes and nucleosome-free regions harboring regulatory proteins along single chromatin fibers, is fundamental to genome function. However, most sequencing methods cannot elucidate this organization at the nucleotide level. Stergachis et al. present an approach, Fiber-seq, that maps chromatin fibers onto the underlying DNA template using methyltransferases to create a kind of stencil in fly and human cells. This method identifies chromatin structure at nearly a single-molecule level and can monitor the position of nucleosomes. Using Fiber-seq, the authors identify how regulatory DNA activation is related to nucleosome positioning and DNA variation. Science , this issue p. 1449
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Single-molecule footprinting methods that use methyltransferases to mark accessible sites can provide quantitative measurements of binding states across individual molecules.
“single-molecule footprinting methods that use methyltransferases to mark accessible sites11–15 can provide quantitative measurements of these binding states across individual molecules”
From Single-molecule states link transcription factor binding to gene expression (2024) · cites this paper as [15]
Transcription factor binding to DNA appears to be very transient.
“While it is clear that enhancers typically favour the more flexible models of sequence organisation, the degree of necessary cooperation between TFs is less obvious, particularly since TF binding to DNA appears to be very transient [113–117].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [117]
Cites
Chromatin modifications and their function
Kouzarides, T. (2007) · Cell · doi:10.1016/j.cell.2007.02.005 · Cited by 10,883 · see citing works
Systematic Localization of Common Disease-Associated Variation in Regulatory DNA
Maurano, M. T., Humbert, R., Rynes, E., Thurman, R. E., Haugen, E., Wang, H., Reynolds, A. P., Sandstrom, R., Qu, H., Brody, J., et al. (2012) · Science · doi:10.1126/science.1222794 · Cited by 3,716 · see citing works
Self-citationWeintraub, H., & Groudine, M. (1976) · Science · doi:10.1126/science.948749 · Cited by 1,809 · see citing works
Fang, G., Munera, D., Friedman, D. I., Mandlik, A., Chao, M. C., Banerjee, O., Feng, Z., Losic, B., Mahajan, M. C., Jabado, O. J., et al. (2012) · Nature Biotechnology · doi:10.1038/nbt.2432 · Cited by 360 · see citing works
Voss, T. C., Schiltz, R. L., Sung, M.-H., Yen, P. M., Stamatoyannopoulos, J. A., Biddie, S. C., Johnson, T. A., Miranda, T. B., John, S., & Hager, G. L. (2011) · Cell · doi:10.1016/j.cell.2011.07.006 · Cited by 307 · see citing works
Self-citationLong-range single-molecule mapping of chromatin accessibility in eukaryotes
Shipony, Z., Marinov, G. K., Swaffer, M. P., Sinnott-Armstrong, N. A., Skotheim, J. M., Kundaje, A., & Greenleaf, W. J. (2020) · Nature Methods · doi:10.1038/s41592-019-0730-2 · Cited by 160 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Methods and applications for single-cell and spatial multi-omics
Vandereyken, K., Sifrim, A., Thienpont, B., & Voet, T. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00580-2 · Cited by 1,244 · see citing works
Segmental duplications and their variation in a complete human genome
Vollger, M. R., Guitart, X., Dishuck, P. C., Mercuri, L., Harvey, W. T., Gershman, A., Diekhans, M., Sulovari, A., Munson, K. M., Lewis, A. P., et al. (2022) · Science · doi:10.1126/science.abj6965 · Cited by 350 · see citing works
Epigenetic patterns in a complete human genome
Gershman, A., Sauria, M. E. G., Guitart, X., Vollger, M. R., Hook, P. W., Hoyt, S. J., Jain, M., Shumate, A., Razaghi, R., Koren, S., et al. (2022) · Science · doi:10.1126/science.abj5089 · Cited by 297 · see citing works
Long-Read DNA Sequencing: Recent Advances and Remaining Challenges
Warburton, P. E., & Sebra, R. P. (2023) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-101722-103045 · Cited by 163 · see citing works
Recent advances in single-cell sequencing technologies
Wen, L., & Tang, F. (2022) · Precision Clinical Medicine · doi:10.1093/pcmedi/pbac002 · Cited by 127 · see citing works
Hold out the genome: a roadmap to solving the cis-regulatory code
de Boer, C. G., & Taipale, J. (2024) · Nature · doi:10.1038/s41586-023-06661-w · Cited by 107 · see citing works
Transcriptional enhancers and their communication with gene promoters
Ray-Jones, H., & Spivakov, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03903-w · Cited by 81 · see citing works
Single-molecule states link transcription factor binding to gene expression
Doughty, B. R., Hinks, M. M., Schaepe, J. M., Marinov, G. K., Thurm, A. R., Rios-Martinez, C., Parks, B. E., Tan, Y., Marklund, E., Dubocanin, D., et al. (2024) · Nature · doi:10.1038/s41586-024-08219-w · Cited by 42 · see citing works
- Authors
- Stergachis, A. B., Debo, B. M., Haugen, E., Churchman, L. S., & Stamatoyannopoulos, J. A.
- Affiliations
- Brigham and Women's Hospital (US)
- Altius Institute for Biomedical Sciences (US)
- Harvard University (US)
- University of Washington (US)
- Corresponding author
- Stergachis, Andrew B.
- Stamatoyannopoulos, John A.
- Venue
- Science
- Published
- 2020-06-26
- Volume
- 368
- Issue
- 6498
- Pages
- 1449-1454
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W3037519049
- Cited by
- 257
- References
- 6
- Citations by year
- 2026: 66 · 2025: 69 · 2024: 36 · 2023: 29 · 2022: 28 · 2021: 23 · 2020: 6
- FWCI
- 7.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Human Genome Research Institute (1UM1HG009444)
- National Institute of General Medical Sciences (GM007748)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- chromatin fiber structure, nucleosome positioning, nucleosome-free regions, chromatin organization
- MeSH terms
- Single Molecule Imaging, Animals, Chromatin, DNA, Drosophila melanogaster, Gene Expression Regulation, Humans, Nucleosomes, Promoter Regions, Genetic, Transcription Factors, Site-Specific DNA-Methyltransferase (Adenine-Specific), K562 Cells, Chromatin Assembly and Disassembly, High-Throughput Nucleotide Sequencing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
