Comparative analysis of metazoan chromatin organization
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A large collection of new modENCODE and ENCODE genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human are analysed; this reveals many conserved features of chromatin organization among the three organisms, as well as notable differences in the composition and locations of repressive chromatin. This study describes numerous new genome-wide chromatin data sets from cell lines and developmental stages of Homo sapiens, Drosophila melanogaster and Caenorhabditis elegans generated by the ENCODE and modENCODE consortia. The results point to many conserved features of chromatin organization among the three organisms, while identifying differences in the composition and locations of repressive chromatin. Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms1,2,3. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal ‘arms’, and centromeres distributed along their lengths4,5. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
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The median distance between the common boundaries was approximately 750 kb, consistent with the reported median TAD size in human cells.
“The median distance between the common boundaries was approximately 750 kb, consistent with the reported median TAD size in human cells4,19 (Extended Data Fig. 1e).”
From Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer (2020) · cites this paper as [19]
Five distinct groups of TADs were identified by k-means clustering of chromatin state coverage: heterochromatin (61), low/quiescent (705), repressed (481), low-active (764) and active (365) domains.
“The obtained matrix was grouped using the k-means clustering approach and five distinct groups of TADs were identified similar to a previous classification of chromatin domains17,19,33. These groups comprised heterochromatin (61), low/quiescent (705), repressed (481), low-active (764) and active (365) domains (Fig. 4a, Supplementary Table 4).”
From Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer (2020) · cites this paper as [19]
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Self-citation
- Authors
- Ho, J. W. K., Jung, Y. L., Liu, T., Alver, B. H., Lee, S., Ikegami, K., Sohn, K.-A., Minoda, A., Tolstorukov, M. Y., Appert, A., Parker, S. C. J., Gu, T., Kundaje, A., Riddle, N. C., Bishop, E., Egelhofer, T. A., Hu, S. S., Alekseyenko, A. A., Rechtsteiner, A., Asker, D., Belsky, J. A., Bowman, S. K., Chen, Q. B., Chen, R. A.-J., Day, D. S., Dong, Y., Dose, A. C., Duan, X., Epstein, C. B., Ercan, S., Feingold, E. A., Ferrari, F., Garrigues, J. M., Gehlenborg, N., Good, P. J., Haseley, P., He, D., Herrmann, M., Hoffman, M. M., Jeffers, T. E., Kharchenko, P. V., Kolasinska-Zwierz, P., Kotwaliwale, C. V., Kumar, N., Langley, S. A., Larschan, E. N., Latorre, I., Libbrecht, M. W., Lin, X., Park, R., Pazin, M. J., Pham, H. N., Plachetka, A., Qin, B., Schwartz, Y. B., Shoresh, N., Stempor, P., Vielle, A., Wang, C., Whittle, C. M., Xue, H., Kingston, R. E., Kim, J. H., Bernstein, B. E., Dernburg, A. F., Pirrotta, V., Kuroda, M. I., Noble, W. S., Tullius, T. D., Kellis, M., MacAlpine, D. M., Strome, S., Elgin, S. C. R., Liu, X. S., Lieb, J. D., Ahringer, J., Karpen, G. H., & Park, P. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- University of North Carolina at Chapel Hill (US)
- Seoul National University (KR)
- Lawrence Berkeley National Laboratory (US)
- University of Cambridge (GB)
- National Institutes of Health (US)
- Washington University in St. Louis (US)
- Broad Institute (US)
- Victor Chang Cardiac Research Institute (AU)
- Boston University (US)
- University of California, Santa Cruz (US)
- Rutgers, The State University of New Jersey (US)
- Duke Medical Center (US)
- Tongji University (CN)
- University of California, Berkeley (US)
- Princess Margaret Cancer Centre (CA)
- Howard Hughes Medical Institute (US)
- Brown University (US)
- University of Washington (US)
- Corresponding author
- MacAlpine, David M.
- Strome, Susan
- Elgin, Sarah C. R.
- Liu, Xiaole Shirley
- Lieb, Jason D.
- Ahringer, Julie
- Karpen, Gary H.
- Park, Peter J.
- ORCID
- Ho, Joshua W. K.
- Jung, Youngsook L.
- Liu, Tao
- Lee, Soohyun
- Ikegami, Kohta
- Sohn, Kyung-Ah
- Minoda, Aki
- Tolstorukov, Michael Y.
- Parker, Stephen C. J.
- Gu, Tingting
- Kundaje, Anshul
- Riddle, Nicole C.
- Rechtsteiner, Andreas
- Asker, Dalal
- Belsky, Jason A.
- Chen, Q. Brent
- Chen, Ron A.-J.
- Epstein, Charles B.
- Ferrari, Francesco
- Garrigues, Jacob M.
- Gehlenborg, Nils
- He, Daniel
- Hoffman, Michael M.
- Jeffers, Tess E.
- Kharchenko, Peter V.
- Langley, Sasha A.
- Larschan, Erica N.
- Latorre, Isabel
- Libbrecht, Maxwell W.
- Lin, Xueqiu
- Pazin, Michael J.
- Qin, Bo
- Schwartz, Yuri B.
- Vielle, Anne
- Wang, Chengyang
- Xue, Huiling
- Kingston, Robert E.
- Kim, Ju Han
- Bernstein, Bradley E.
- Dernburg, Abby F.
- Kuroda, Mitzi I.
- Noble, William S.
- Tullius, Thomas D.
- Kellis, Manolis
- MacAlpine, David M.
- Strome, Susan
- Elgin, Sarah C. R.
- Ahringer, Julie
- Karpen, Gary H.
- Park, Peter J.
- Venue
- Nature
- Published
- 2014-08-27
- Volume
- 512
- Issue
- 7515
- Pages
- 449-452
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4227084
- OpenAlex
- W1981516407
- Cited by
- 390
- References
- 27
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 21 · 2023: 30 · 2022: 25 · 2021: 58 · 2020: 24 · 2019: 42 · 2018: 31 · 2017: 45 · 2016: 35 · 2015: 49 · 2014: 11
- FWCI
- 19.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Open Scholarship Institutional Repository (Washington University in St. Louis) (submittedVersion, cc-by-nc-sa)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Science Foundation (1122374, 0000994)
- Howard Hughes Medical Institute
- Wellcome Trust (101863, 54523, 101863/Z/13/Z, 092096)
- National Natural Science Foundation of China (31028011, 1122374)
- National Institutes of Health (5u54hg004570-04, 1122374, U54-CA121852)
- National Human Genome Research Institute (U01HG004258, U01HG004270, K99HG006259, U01HG004279, U01HG004695, U54HG006991, U54-HG004570, R01HG004037, T32HG002295)
- National Cancer Institute (U54CA121852)
- National Institute of General Medical Sciences (T32GM071340, R01GM098461, R37GM048405)
- National Institute of Biomedical Imaging and Bioengineering (RL9EB008539)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- chromatin organization, comparative genomics, histone modifications, repressive chromatin, heterochromatin, topologically associating domains, nucleosome positioning, DNA replication, enhancers, promoter, Caenorhabditis elegans, Drosophila melanogaster, human, modENCODE, ENCODE
- MeSH terms
- Animals, Cell Line, Centromere, Chromatin, DNA Replication, Drosophila melanogaster, Enhancer Elements, Genetic, Heterochromatin, Histones, Humans, Nucleosomes, Promoter Regions, Genetic, Species Specificity, Caenorhabditis elegans, Nuclear Lamina, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Molecular Sequence Annotation
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