The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development
Open accessAbstract
Conservation of the vertebrate body plan has been attributed to the evolutionary stability of gene-regulatory networks (GRNs). We describe a regulatory circuit made up of Gata2, Fli1, and Scl/Tal1 and their enhancers, Gata2-3 , Fli1 +12, and Scl +19, that operates during specification of hematopoiesis in the mouse embryo. We show that the Fli1 +12 enhancer, like the Gata2-3 and Scl +19 enhancers, targets hematopoietic stem cells (HSCs) and relies on a combination of Ets, Gata, and E-Box motifs. We show that the Gata2-3 enhancer also uses a similar cluster of motifs and that Gata2, Fli1, and Scl are expressed in embryonic day-11.5 dorsal aorta where HSCs originate and in fetal liver where they multiply. The three HSC enhancers in these tissues and in ES cell-derived hemangioblast equivalents are bound by each of these transcription factors (TFs) and form a fully connected triad that constitutes a previously undescribed example of both this network motif in mammalian development and a GRN kernel operating during the specification of a mammalian stem cell.
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“A recursively wired triple feedback circuit has been proposed as a kernel underlying the pluripotential state of endothelial/hematopoietic precursors that arise in vertebrate development (Pimanda et al., 2007).”
From Evolution of Gene Regulatory Networks Controlling Body Plan Development (2011) · cites this paper as Pimanda et al., 2007
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“This sub-circuit consists of three positively active genes. There are no cross-regulating repressors in this sub-circuit, and the three genes are linked by multiple positive auto- and cross-regulatory linkages.”
From Emerging properties of animal gene regulatory networks (2010) · cites this paper as [28]
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Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells
Boyer, L. A., Lee, T. I., Cole, M. F., Johnstone, S. E., Levine, S. S., Zucker, J. P., Guenther, M. G., Kumar, R. M., Murray, H. L., Jenner, R. G., et al. (2005) · Cell · doi:10.1016/j.cell.2005.08.020 · Cited by 4,505
An Introduction to Systems Biology: Design Principles of Biological Circuits
Alon, U. (2006) · doi:10.1201/9781420011432 · Cited by 2,825
Okuda, T., van Deursen, J., Hiebert, S. W., Grosveld, G., & Downing, J. R. (1996) · Cell · doi:10.1016/s0092-8674(00)80986-1 · Cited by 1,856
Weissman, I. L. (2000) · Cell · doi:10.1016/s0092-8674(00)81692-x · Cited by 1,827
A common precursor for hematopoietic and endothelial cells
Choi, K., Kennedy, M., Kazarov, A. R., Papadimitriou, J. C., & Keller, G. M. (1998) · Development · doi:10.1242/dev.125.4.725 · Cited by 1,435
An early haematopoietic defect in mice lacking the transcription factor GATA-2
Tsai, F., Keller, G. M., Kuo, F. C., Weiss, M. J., Chen, J., Rosenblatt, M., Alt, F. W., & Orkin, S. H. (1994) · Nature · doi:10.1038/371221a0 · Cited by 1,419
Transcription regulation and animal diversity
Levine, M., & Tjian, R. (2003) · Nature · doi:10.1038/nature01763 · Cited by 1,309
Gene Regulatory Networks and the Evolution of Animal Body Plans
Davidson, E. H., & Erwin, D. H. (2006) · Science · doi:10.1126/science.1113832 · Cited by 1,207
Wang, Q., Stacy, T., Binder, M., Marin-Padilla, M., Sharpe, A. H., & Speck, N. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.8.3444 · Cited by 1,178
An Introduction to Systems Biology: Design Principles of Biological Circuits
Alon, U. (2019) · doi:10.1201/9780429283321 · Cited by 955
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- M Varterasian, S Lipkowitz, I Karsch-Mizrachi, B Paterson, I Kirsch Cell Growth Differ 4, 885–889 (1993).
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Loke, J. C. T., Ptasinska, A., Imperato, M. R., Assi, S. A., Cauchy, P., Cowell, I. G., Heidenreich, O. T., Raghavan, M., Delwel, R., Cockerill, P., et al. (2016) · Klinische Pädiatrie · doi:10.1055/s-0036-1582520
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Cui, H., Wang, Y., Huang, H., Yu, W., Bai, M., Zhang, L., Bryan, B. A., Wang, Y., Luo, J., Li, D., et al. (2014)
Genetics and functional characterization of GATA2: a novel cancer gene in familial leukaemia.
Chong, C. (2013) · Adelaide Research & Scholarship (AR&S) (University of Adelaide)
Méndez‐Ferrer, S. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.732563533.793575319
Butler, J. M. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733517039.793569471
Subramanian, S., Thoms, J., Huang, Y., Cornejo, P., Koch, F. C., Jacquelin, S., Shen, S., Song, E., Joshi, S. M., Brownlee, C., et al. (2023) · bioRxiv · doi:10.1101/2023.04.18.537282
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FAIRsharing record for: BloodChIP Xtra
FAIRsharing Team, et al. (2024) · FAIRsharing.org · doi:10.25504/fairsharing.5ad8f7
Metadata
- Authors
- Pimanda, J. E., Ottersbach, K., Knezevic, K., Kinston, S., Chan, W. Y. I., Wilson, N. K., Landry, J.-R., Wood, A. D., Kolb-Kokocinski, A., Green, A. R., Tannahill, D., Lacaud, G., Kouskoff, V., & Göttgens, B.
- Affiliations
- University of Cambridge (GB)
- The Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom; and
- Wellcome Sanger Institute (GB)
- Cancer Research UK Manchester Institute (GB)
- Paterson Institute for Cancer Research, Manchester M20 4BX, United Kingdom
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-11-06
- Volume
- 104
- Issue
- 45
- Pages
- 17692-17697
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2077040
- OpenAlex
- W1996351707
- Cited by
- 228
- References
- 46
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 3 · 2023: 11 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 9 · 2017: 8 · 2016: 19 · 2015: 16 · 2014: 17 · 2013: 22 · 2012: 18
- FWCI
- 10.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Wellcome Trust
- Kay Kendall Leukaemia Fund
- University of Oxford
- Directorate for Biological Sciences
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- National Health and Medical Research Council
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- GATA2, FLI1, SCL/TAL1, gene regulatory networks, hematopoietic stem cells, enhancers, transcription factor binding motifs, E-box motifs, dorsal aorta, fetal liver, hemangioblasts, embryonic stem cells, hematopoietic specification, network motifs
- MeSH terms
- T-Cell Acute Lymphocytic Leukemia Protein 1, Animals, Binding Sites, Blood Vessels, Embryo, Mammalian, Enhancer Elements, Genetic, Gene Expression Regulation, Hematopoiesis, Hematopoietic Stem Cells, Proto-Oncogene Proteins, GATA2 Transcription Factor, Mice, Proto-Oncogene Protein c-fli-1, Basic Helix-Loop-Helix Proteins
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