The DOI matches its Crossref record; 55 of the 57 references it cites were found in a registry or an index.
Genome-wide analysis of transcriptional regulators in human HSPCs reveals a densely interconnected network of coding and noncoding genes
Abstract
Genome-wide combinatorial binding patterns for key transcription factors (TFs) have not been reported for primary human hematopoietic stem and progenitor cells (HSPCs), and have constrained analysis of the global architecture of molecular circuits controlling these cells. Here we provide high-resolution genome-wide binding maps for a heptad of key TFs (FLI1, ERG, GATA2, RUNX1, SCL, LYL1, and LMO2) in human CD34(+) HSPCs, together with quantitative RNA and microRNA expression profiles. We catalog binding of TFs at coding genes and microRNA promoters, and report that combinatorial binding of all 7 TFs is favored and associated with differential expression of genes and microRNA in HSPCs. We also uncover a previously unrecognized association between FLI1 and RUNX1 pairing in HSPCs, we establish a correlation between the density of histone modifications that mark active enhancers and the number of overlapping TFs at a peak, we demonstrate bivalent histone marks at promoters of heptad target genes in CD34(+) cells that are poised for later expression, and we identify complex relationships between specific microRNAs and coding genes regulated by the heptad. Taken together, these data reveal the power of integrating multifactor sequencing of chromatin immunoprecipitates with coding and noncoding gene expression to identify regulatory circuits controlling cell identity.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
In the citing paper
“For instance, the combinatorial occupancy of chromatin by multiple master TFs has revealed regulatory networks that are important for hematopoiesis (Beck et al., 2013; Schütte et al., 2016), as well as key regulatory elements necessary for HSC self-renewal (Bahr et al., 2018).”
From Unraveling Hematopoiesis through the Lens of Genomics (2020) · cites this paper as Beck et al., 2013
Citations
Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072
Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382
Lewis, B. P., Burge, C. B., & Bartel, D. P. (2005) · Cell · doi:10.1016/j.cell.2004.12.035 · Cited by 11,855
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,682
Fitting a mixture model by expectation maximization to discover motifs in biopolymers.
Bailey, T. L., & Elkan, C. (1994) · PubMed · Cited by 4,982
GREAT improves functional interpretation of cis-regulatory regions
McLean, C. Y., Bristor, D., Hiller, M., Clarke, S. L., Schaar, B. T., Lowe, C. B., Wenger, A. M., & Bejerano, G. (2010) · Nature Biotechnology · doi:10.1038/nbt.1630 · Cited by 4,502
Histone H3K27ac separates active from poised enhancers and predicts developmental state
Creyghton, M. P., Cheng, A. W., Welstead, G. G., Kooistra, T., Carey, B. W., Steine, E. J., Hanna, J., Lodato, M. A., Frampton, G. M., Sharp, P. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016071107 · Cited by 4,302
FIMO: scanning for occurrences of a given motif
Grant, C. E., Bailey, T. L., & Noble, W. S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr064 · Cited by 4,247
MicroRNA targets in Drosophila
Enright, A. J., John, B., Gaul, U., Tuschl, T., Sander, C., & Marks, D. S. (2003) · Genome Biology · doi:10.1186/gb-2003-5-1-r1 · Cited by 3,597
Network motifs: theory and experimental approaches
Alon, U. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2102 · Cited by 3,279
Direct conversion of fibroblasts to functional neurons by defined factors
Vierbuchen, T., Ostermeier, A., Pang, Z. P., Kokubu, Y., Südhof, T. C., & Wernig, M. (2010) · Nature · doi:10.1038/nature08797 · Cited by 3,017
A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
Akashi, K., Traver, D., Miyamoto, T., & Weissman, I. L. (2000) · Nature · doi:10.1038/35004599 · Cited by 2,617
Hematopoiesis: An Evolving Paradigm for Stem Cell Biology
Orkin, S. H., & Zon, L. I. (2008) · Cell · doi:10.1016/j.cell.2008.01.025 · Cited by 2,570
Identification of Clonogenic Common Lymphoid Progenitors in Mouse Bone Marrow
Kondo, M., Weissman, I. L., & Akashi, K. (1997) · Cell · doi:10.1016/s0092-8674(00)80453-5 · Cited by 2,253
ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia
Landt, S. G., Marinov, G. K., Kundaje, A., Kheradpour, P., Pauli, F., Batzoglou, S., Bernstein, B. E., Bickel, P., Brown, J. B., Cayting, P., et al. (2012) · Genome Research · doi:10.1101/gr.136184.111 · Cited by 2,033
The NIH Roadmap Epigenomics Mapping Consortium
Bernstein, B. E., Stamatoyannopoulos, J. A., Costello, J. F., Ren, B., Milosavljevic, A., Meissner, A., Kellis, M., Marra, M. A., Beaudet, A. L., Ecker, J. R., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt1010-1045 · Cited by 1,892
Argonaute HITS-CLIP decodes microRNA–mRNA interaction maps
Chi, S. W., Zang, J. B., Mele, A., & Darnell, R. B. (2009) · Nature · doi:10.1038/nature08170 · Cited by 1,791
Pioneer transcription factors: establishing competence for gene expression
Zaret, K. S., & Carroll, J. S. (2011) · Genes & Development · doi:10.1101/gad.176826.111 · Cited by 1,589
High-Resolution Mapping and Characterization of Open Chromatin across the Genome
Boyle, A. P., Davis, S., Shulha, H. P., Meltzer, P., Margulies, E. H., Weng, Z., Furey, T. S., & Crawford, G. E. (2008) · Cell · doi:10.1016/j.cell.2007.12.014 · Cited by 1,415
Connecting microRNA Genes to the Core Transcriptional Regulatory Circuitry of Embryonic Stem Cells
Marson, A., Levine, S. S., Cole, M. F., Frampton, G. M., Brambrink, T., Johnstone, S. E., Guenther, M. G., Johnston, W. K., Wernig, M., Newman, J. J., et al. (2008) · Cell · doi:10.1016/j.cell.2008.07.020 · Cited by 1,405
Identification of Flt3+ Lympho-Myeloid Stem Cells Lacking Erythro-Megakaryocytic Potential
Adolfsson, J., Månsson, R., Buza-Vidas, N., Hultquist, A., Liuba, K., Jensen, C. T., Bryder, D., Yang, L., Borge, O. J., Thorén, L., et al. (2005) · Cell · doi:10.1016/j.cell.2005.02.013 · Cited by 1,323
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
Stem cell gene expression programs influence clinical outcome in human leukemia
Eppert, K., Takenaka, K., Lechman, E. R., Waldron, L., Nilsson, B., van Galen, P., Metzeler, K. H., Poeppl, A. G., Ling, V., Beyene, J., et al. (2011) · Nature Medicine · doi:10.1038/nm.2415 · Cited by 1,071
Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age
Pang, W. W., Price, E. A., Sahoo, D., Beerman, I., Maloney, W. J., Rossi, D. J., Schrier, S. L., & Weissman, I. L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116110108 · Cited by 991
Densely Interconnected Transcriptional Circuits Control Cell States in Human Hematopoiesis
Novershtern, N., Subramanian, A., Lawton, L. N., Mak, R. H., Haining, W. N., McConkey, M. E., Habib, N., Yosef, N., Chang, C. Y., Shay, T., et al. (2011) · Cell · doi:10.1016/j.cell.2011.01.004 · Cited by 942
Wilson, N. K., Foster, S. D., Wang, X., Knezevic, K., Schütte, J., Kaimakis, P., Chilarska, P. M., Kinston, S., Ouwehand, W. H., Dzierzak, E., et al. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.07.016 · Cited by 728
Bryne, J. C., Valen, E., Tang, M. E., Marstrand, T. T., Winther, O., da Piedade, I., Krogh, A., Lenhard, B., & Sandelin, A. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm955 · Cited by 702
Cui, K., Zang, C., Roh, T., Schones, D. E., Childs, R. W., Peng, W., & Zhao, K. (2009) · Cell stem cell · doi:10.1016/j.stem.2008.11.011 · Cited by 646
Long-Term Propagation of Distinct Hematopoietic Differentiation Programs In Vivo
Dykstra, B. J., Kent, D. G., Bowie, M. B., McCaffrey, L., Hamilton, M. J., Lyons, K., Lee, S.-J., Brinkman, R. R., & Eaves, C. J. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.05.015 · Cited by 632
Ichikawa, M., Asai, T., Saito, T., Yamamoto, G., Seo, S., Yamazaki, I., Yamagata, T., Mitani, K., Chiba, S., Hirai, H., et al. (2004) · Nature Medicine · doi:10.1038/nm997 · Cited by 596
Gentles, A. J. (2010) · JAMA · doi:10.1001/jama.2010.1862 · Cited by 410
Garber, M., Yosef, N., Goren, A., Raychowdhury, R., Thielke, A., Guttman, M., Robinson, J., Minie, B., Chevrier, N., Itzhaki, Z., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.07.030 · Cited by 369
Binding of disparate transcriptional activators to nucleosomal DNA is inherently cooperative
Adams, C. C., & Workman, J. L. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.3.1405 · Cited by 298
Tijssen, M. R., Cvejic, A., Joshi, A., Hannah, R., Ferreira, R., Forrai, A., Bellissimo, D. C., Oram, S. H., Smethurst, P. A., Wilson, N. K., et al. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.04.008 · Cited by 296
A Transcription Factor Collective Defines Cardiac Cell Fate and Reflects Lineage History
Junion, G., Spivakov, M., Girardot, C., Braun, M., Gustafson, E. H., Birney, E., & Furlong, E. E. M. (2012) · Cell · doi:10.1016/j.cell.2012.01.030 · Cited by 257
Runx1-mediated hematopoietic stem-cell emergence is controlled by a Gata/Ets/SCL-regulated enhancer
Nottingham, W. T., Jarratt, A., Burgess, M. O., Speck, C. L., Cheng, J., Prabhakar, S., Rubin, E., Li, P.-S., Sloane‐Stanley, J., Kong-a-San, J., et al. (2007) · Blood · doi:10.1182/blood-2007-07-100883 · Cited by 249
A HaemAtlas: characterizing gene expression in differentiated human blood cells
Watkins, N. A., Gusnanto, A., de Bono, B., De, S., Miranda‐Saavedra, D., Hardie, D. L., Angenent, W. G. J., Attwood, A., Ellis, P. D., Erber, W. N., et al. (2009) · Blood · doi:10.1182/blood-2008-06-162958 · Cited by 242
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., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707045104 · Cited by 228
Self-citationdoRiNA: a database of RNA interactions in post-transcriptional regulation
Anders, G., Mackowiak, S. D., Jens, M., Maaskola, J., Kuntzagk, A., Rajewsky, N., Landthaler, M., & Dieterich, C. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr1007 · Cited by 202
Fli1 Acts at the Top of the Transcriptional Network Driving Blood and Endothelial Development
Liu, F., Walmsley, M. E., Rodaway, A., & Patient, R. K. (2008) · Current Biology · doi:10.1016/j.cub.2008.07.048 · Cited by 182
Chromatin Structure and Gene Regulation in the Immune System
Smale, S. T., & Fisher, A. G. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.100301.064739 · Cited by 176
MicroRNA Expression and Regulation in Human, Chimpanzee, and Macaque Brains
Hu, H. Y., Guo, S., Xi, J., Yan, Z., Fu, N., Zhang, X., Menzel, C., Liang, H., Yang, H., Zhao, M., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002327 · Cited by 130
Thoms, J. A. I., Birger, Y., Foster, S., Knezevic, K., Kirschenbaum, Y., Chandrakanthan, V., von Jonquières, G., Spensberger, D., Wong, J. W. H., Oram, S. H., et al. (2011) · Blood · doi:10.1182/blood-2010-12-317990 · Cited by 99
AGata2intronic enhancer confers its pan-endothelia-specific regulation
Khandekar, M. J., Brandt, W. D., Zhou, Y., Dagenais, S. L., Glover, T. W., Suzuki, N., Shimizu, R., Yamamoto, M. P., Lim, K.-C., & Engel, J. D. (2007) · Development · doi:10.1242/dev.001297 · Cited by 92
SCL is required for normal function of short-term repopulating hematopoietic stem cells
Curtis, D. J., Hall, M. A., van Stekelenburg, L., Robb, L. G., Jane, S. M., & Begley, C. G. (2004) · Blood · doi:10.1182/blood-2003-09-3202 · Cited by 89
Chan, W. Y. I., Follows, G., Lacaud, G., Pimanda, J. E., Landry, J., Kinston, S., Knezevic, K., Piltz, S., Donaldson, I. J., Gambardella, L., et al. (2006) · Blood · doi:10.1182/blood-2006-05-023226 · Cited by 84
MicroRNA-146a disrupts hematopoietic differentiation and survival
Starczynowski, D. T., Kuchenbauer, F., Wegrzyn, J., Rouhi, A., Petriv, O., Hansen, C. L., Humphries, R. K., & Karsan, A. (2011) · Experimental Hematology · doi:10.1016/j.exphem.2010.09.011 · Cited by 84
Diffner, E., Beck, D., Gudgin, E. J., Thoms, J. A. I., Knezevic, K., Pridans, C., Foster, S., Goode, D. K., Lim, W. K., Boelen, L., et al. (2013) · Blood · doi:10.1182/blood-2012-07-446120 · Cited by 82
Landry, J., Bonadies, N., Kinston, S., Knezevic, K., Wilson, N. K., Oram, S. H., Janes, M. E., Piltz, S., Hammett, M., Carter, J., et al. (2009) · Blood · doi:10.1182/blood-2008-11-187757 · Cited by 77
Gene regulatory networks governing haematopoietic stem cell development and identity
Pimanda, J. E., & Göttgens, B. (2010) · The International Journal of Developmental Biology · doi:10.1387/ijdb.093038jp · Cited by 55
Ogilvy, S., Ferreira, R., Piltz, S., Bowen, J. M., Göttgens, B., & Green, A. R. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00931-07 · Cited by 44
Narula, J., Williams, C. J., Tiwari, A., Marks-Bluth, J., Pimanda, J. E., & Igoshin, O. A. (2013) · Developmental Biology · doi:10.1016/j.ydbio.2013.04.016 · Cited by 23
Cited by
Sorted by citations
Giustacchini, A., Thongjuea, S., Barkas, N., Woll, P. S., Povinelli, B. J., Booth, C. A. G., Sopp, P., Norfo, R., Rodriguez-Meira, A., Ashley, N., et al. (2017) · Nature Medicine · doi:10.1038/nm.4336 · Cited by 403
Global transcriptome analyses of human and murine terminal erythroid differentiation
An, X., Schulz, V., Li, J., Wu, K., Liu, J., Xue, F., Hu, J., Mohandas, N., & Gallagher, P. G. (2014) · Blood · doi:10.1182/blood-2014-01-548305 · Cited by 361
Huang, J., Liu, X., Li, D., Shao, Z., Cao, H., Zhang, Y., Trompouki, E., Bowman, T. V., Zon, L. I., Yuan, G., et al. (2016) · Developmental Cell · doi:10.1016/j.devcel.2015.12.014 · Cited by 247
“We also re-analyzed 45 previously published ChIP-seq datasets of TFs and chromatin regulators obtained in the same cell populations (Abraham et al., 2013; Beck et al., 2013; Dogan Figure 3.”
MethodHaematopoietic and immune defects associated with GATA2 mutation
Collin, M. P., Dickinson, R. E., & Bigley, V. (2015) · British Journal of Haematology · doi:10.1111/bjh.13317 · Cited by 237
“…adult haematopoiesis, GATA2 is required for HSC survival and self-renewal, interacting with a complex network of transcription factors that specify early lineage commitment, including SPI1 (PU.1), FLI1, TAL1 (SCL), LMO2 and RUNX1, among others (Dore et al, 2012; Beck et al, 2013; May et al, 2013).”
BackgroundCai, X., Gao, L., Teng, L., Ge, J., Oo, Z. M., Kumar, A. R., Gilliland, D. G., Mason, P. J., Tan, K., & Speck, N. A. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.06.002 · Cited by 237
“We analyzed the genome-wide occupancy of RUNX1 using previously published chromatin immunoprecipitation sequencing (ChIP-seq) data generated in human CD34+ HSPCs (Beck et al., 2013).”
Influential
Metadata
- Authors
- Beck, D., Thoms, J. A. I., Perera, D., Schütte, J., Unnikrishnan, A., Knezevic, K., Kinston, S. J., Wilson, N. K., O’Brien, T. A., Göttgens, B., Wong, J. W. H., & Pimanda, J. E.
- Affiliations
- UNSW Sydney (AU)
- University of Cambridge (GB)
- Centre for Children’s Cancer & Blood Disorders, Sydney Children’s Hospital, Sydney, Australia;
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2013-10-03
- Volume
- 122
- Issue
- 14
- Pages
- e12-e22
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1976712740
- Cited by
- 133
- References
- 57
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 9 · 2023: 12 · 2022: 6 · 2021: 15 · 2020: 16 · 2019: 12 · 2018: 7 · 2017: 12 · 2016: 15 · 2015: 10 · 2014: 14 · 2013: 1
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- UTS ePRESS (University of Technology Sydney) (submittedVersion)
- Funders
- University of California, Santa Cruz
- Wellcome Trust (079249, 100140)
- Cancer Research UK (12765)
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (G0900729/1)
- University of New South Wales
- Medical Research Council (MC_PC_12009)
- Biotechnology and Biological Sciences Research Council (BB/I00050X/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- hematopoietic stem and progenitor cells, transcription factors, FLI1, RUNX1, GATA2, ERG, SCL, LYL1, LMO2, microRNA promoters, CD34+ cells, gene regulatory networks, cell identity, chromatin immunoprecipitation
- MeSH terms
- Cell Differentiation, Flow Cytometry, Hematopoiesis, Hematopoietic Stem Cells, Humans, Transcription Factors, Transcription, Genetic, Cluster Analysis, RNA, Untranslated, Chromatin Immunoprecipitation, Genome-Wide Association Study
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
