Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome
Open accessAbstract
Chromosomal Mapping: The conformation of the genome in the nucleus and contacts between both proximal and distal loci influence gene expression. In order to map genomic contacts, Lieberman-Aiden et al. (p. 289 , see the cover) developed a technique to allow the detection of all interactions between genomic loci in the eukaryotic nucleus followed by deep sequencing. This technology was used to map the organization of the human genome and to examine the spatial proximity of chromosomal loci at one megabase resolution. The map suggests that the genome is partitioned into two spatial compartments that are related to local chromatin state and whose remodeling correlates with changes in the chromatin state.
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Contacts from active chromatin and heterochromatin regions appear largely segregated into separate compartments (A and B).
“contacts from active chromatin and heterochromatin regions appear largely segregated into separate compartments (referred to as A and B, respectively) [272].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [272]
Chromosomal contacts follow the law of constrained Brownian motion, with contact probabilities showing a strong power-law dependence on linear genomic distance.
“Chromosomal contacts follow the law of constrained Brownian motion (reviewed in [465]), with the contact probabilities showing a strong power–law dependence on the “linear” genomic distance [272, 466].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [272]
Calibration techniques such as spike-in normalization in RNA-seq and ChIP-seq have made absolute quantification of genomics experiments possible.
“This is an intrinsic limitation of all genomics methods, in which the signal is quantified from sequencing read counts, but calibration techniques such as spike-in normalization in RNA-seq52 and ChIP-seq53–55 have made absolute quantification of genomics experiments possible.”
From Genome-wide absolute quantification of chromatin looping (2026) · cites this paper as [52]
Our copy describes Hi-C sequencing and a contact matrix based on read counts (Abstract, page unavailable), but does not address spike-in normalization or absolute quantification in RNA-seq or ChIP-seq. Searches for those terms and for calibration or internal standards found no supporting passage. (LLM, conf=0.75)
Experimental — accuracy not yet measuredThe second mechanism is cohesin-independent compartmentalization of chromatin intervals with similar histone marks.
“The second mechanism is the cohesin-independent compartmentalization of chromatin intervals with similar histone marks (Lieberman-Aiden et al., 2009; Rao et al., 2014).”
From Cohesin Loss Eliminates All Loop Domains (2017) · cites this paper as Lieberman-Aiden et al., 2009
The A compartment is largely localized to the nuclear interior, while the B compartment is tethered to the nuclear periphery by Lamin B1.
“While the A compartment is largely localized to the nuclear interior, the B compartment is tethered to the nuclear periphery by Lamin B1”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [91]
Interactions between domains give rise to two main types of spatial compartments referred to as A and B.
“At larger scales, interactions between domains are thought to give rise to two main types of spatial compartments referred to as “A” and “B” (Lieberman-Aiden et al., 2009)”
From Multiscale 3D Genome Rewiring during Mouse Neural Development (2017) · cites this paper as Lieberman-Aiden et al., 2009
Active chromatin tends to associate with active chromatin and vice versa, giving rise to a plaid pattern in Hi-C maps.
“In mammalian nuclei, active chromatin tends to associate with active chromatin and vice versa giving rise to a “plaid” pattern in maps obtained by genome-wide chromosome conformation capture studies (Hi-C).5”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [5]
Genome-wide, high-resolution understanding of chromosome cell-cycle dynamics is still limited by current technologies.
“genome-wide, high-resolution understanding of chromosome cell-cycle dynamics11 is still limited by current technologies”
From Cell-cycle dynamics of chromosomal organization at single-cell resolution (2017) · cites this paper as [2]
Hi-C records pairs of genomic loci at close proximity, and certain pairs emerge close in three dimensions although separated at large nucleotide distances along the linear chromosome.
“Moving from proteins to DNA, the family of techniques known as chromosome conformation capture, including 3C (Dekker et al., 2002) and Hi-C (Lieberman-Aiden et al., 2009), record pairs of genomic loci that are at close proximity.”
From Mapping the multiscale structure of biological systems (2021) · cites this paper as Lieberman-Aiden et al., 2009
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- Authors
- Lieberman-Aiden, E., van Berkum, N. L., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B. R., Sabo, P. J., Dorschner, M. O., Sandstrom, R., Bernstein, B., Bender, M. A., Groudine, M., Gnirke, A., Stamatoyannopoulos, J., Mirny, L. A., Lander, E. S., & Dekker, J.
- Affiliations
- Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), MA 02139, USA.
- Program in Gene Function and Expression and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
- Broad Institute (US)
- Harvard–MIT Division of Health Sciences and Technology (US)
- University of Washington (US)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Lander, Eric S.
- Dekker, Job
- ORCID
- Venue
- Science
- Published
- 2009-10-09
- Volume
- 326
- Issue
- 5950
- Pages
- 289-293
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2858594
- OpenAlex
- W2090037139
- Cited by
- 8,898
- References
- 36
- Citations by year
- 2026: 496 · 2025: 668 · 2024: 744 · 2023: 759 · 2022: 757 · 2021: 906 · 2020: 788 · 2019: 677 · 2018: 600 · 2017: 482 · 2016: 401 · 2015: 346 · 2014: 286 · 2013: 298 · 2012: 293
- FWCI
- 91.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship@UMassChan (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL06544)
- National Human Genome Research Institute (U54HG004592, HG003143, R01HG003143, T32HG002295)
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK044746, R37DK44746)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- Hi-C, 3D genome organization, long-range chromatin interactions, chromosome territories, chromatin conformation
- MeSH terms
- Biotin, Cell Line, Transformed, Cell Nucleus, Chromatin, Chromosomes, Human, DNA, Humans, Models, Molecular, Monte Carlo Method, Nucleic Acid Conformation, Protein Conformation, Gene Library, Genome, Human, In Situ Hybridization, Fluorescence, Sequence Analysis, DNA, Computational Biology, Principal Component Analysis, Chromatin Immunoprecipitation
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