Cited by 8,898Genomics and Chromatin DynamicsChromosomal and Genetic VariationsGenomic variations and chromosomal abnormalities

Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome

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Lieberman-Aiden, Erez, van Berkum, Nynke L., Williams, Louise, Imakaev, Maxim, Ragoczy, Tobias, Telling, Agnes, Amit, Ido, Lajoie, Bryan R. +11 more·2009·Science

Abstract

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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Crossref · 10.1126/science.1181369

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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].”
  • 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].”
  • 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 measured
  • The 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”

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Research works printed but not linked: 3

  1. [25]Münkel C Langowski J Physical Review E 1998 57 5888
  2. [28]Grosberg A Rabin Y Havlin S Neer A EPL (Europhysics Letters) 1993 373
  3. [37]Hi-C Sequence data has been deposited in the Genbank database (http://www.ncbi.nlm.nih.gov/Genbank/), Accession no. ###. Expression results are available at GEO (http://www.ncbi.nlm.nih.gov/geo/), Accession no. ###. ChIP-Seq data is available at the UCSC Browser (http://genome.ucsc.edu/). Additional visualizations are available at http://hic.umassmed.edu.

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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
Venue
Science
Published
2009-10-09
Volume
326
Issue
5950
Pages
289-293
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
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
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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