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
Cited by
Sorted by citations
Items 101–134 of 134
Molecular Landscapes and Models of Acute Erythroleukemia
Fagnan, A., Piqué‐Borràs, M., Tauchmann, S., Mercher, T., & Schwaller, J. (2021) · HemaSphere · doi:10.1097/hs9.0000000000000558 · Cited by 10
A distinct epigenetic program underlies the 1;7 translocation in myelodysplastic syndromes
Fernandez, A. G. L., Crescenzi, B., Pierini, V., Battista, V. D., Barba, G., Pellanera, F., Giacomo, D. D., Roti, G., Piazza, R., Adelman, E. R., et al. (2019) · Leukemia · doi:10.1038/s41375-019-0433-9 · Cited by 8
“In order to analyze the potential recruitment of transcriptional repressors that could be responsible for gene silencing, we intersected DMRs and extracted promoter position from the identified downregulated genes between dic(1;7) and controls with ChIP-seq data generated in CD34 cells for CTCF [21], one of the most w…”
Dysregulated MAPK signaling pathway in acute myeloid leukemia with RUNX1 mutations
He, M., Jia, Y., Wang, Y., & Cai, X. (2022) · Expert Review of Hematology · doi:10.1080/17474086.2022.2108015 · Cited by 8
“We found that in human CD34 cord blood cells [31], more than 61% MAPKenes (172/294) had RUNX1 binding peaks within 10kb of their promoters (Figure 4(c)).”
BackgroundKugler, E., Madiwale, S., Yong, D., Thoms, J. A. I., Birger, Y., Sykes, D. B., Schmoellerl, J., Drakul, A., Priebe, V., Yassin, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41067-2 · Cited by 8
Katsumura, K. R., Liu, P., Kim, J.-A., Mehta, C., & Bresnick, E. H. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2317147121 · Cited by 7
“GATA2 occupies thousands of chromatin sites (19, 22, 34–36), but this is the only example of a GATA2 - regulated enhancer, other than two Gata2 enhancers (12, 37–40), that is a vital mediator of GATA2 - dependent functions in HSPCs. Surprisingly, this mechanism, which establishes the genetic…”
InfluentialNasrallah, R., Fast, E. M., Kartalaei, P. S., Knezevic, K., Eliades, A., Patel, R., Thambyrajah, R., Unnikrishnan, A., Thoms, J. A. I., Beck, D., et al. (2016) · Blood · doi:10.1182/blood-2016-02-697870 · Cited by 7
“A number of regulatory elements of hematopoietic transcription factors (TFs) have previously been shown to direct reporter expression to developing blood cells in the mouse embryo and include enhancers of Scl, Runx1,Gata2, Erg, Fli1, Lmo2, and Lyl1, which also form a recursive circuit in human adult HSCs.(12) The Runx…”
InfluentialKong, X., Simon, L. M., Holinstat, M. A., Shaw, C., Bray, P. F., & Edelstein, L. C. (2017) · Thrombosis and Haemostasis · doi:10.1160/th16-09-0692 · Cited by 5
“(C) ChIPSeq data from CD34 and K562 cells indicating histone H3 monomethylated on lysine 4 (H3K4me1), a marker of enhancer regions (2, 3, 13-15) (Table 2).”
MethodOverexpression of PTP4A3 in ETV6-RUNX1 acute lymphoblastic leukemia
Grönroos, T., Teppo, S., Mehtonen, J., Laukkanen, S., Liuksiala, T., Nykter, M., Heinäniemi, M., & Lohi, O. (2016) · Leukemia Research · doi:10.1016/j.leukres.2016.12.005 · Cited by 4
Weß, L., & Schnieders, F. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.145 · Cited by 4
Zhou, Y., Mao, B., Chen, Y., Xue, Y., Chen, B., Zhang, Y., & Ma, F. (2020) · Blood Science · doi:10.1097/bs9.0000000000000040 · Cited by 3
Hematopoietic Stem Cell Biology
Rossmann, M. P., Orkin, S. H., & Chute, J. P. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-35762-3.00009-3 · Cited by 3
Tsakanikas, P., Manatakis, D. V., & Manolakos, E. S. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/264671 · Cited by 3
To switch or not to switch: PU.1 expression is the question
Thoms, J. A. I., Pimanda, J. E., & Heidenreich, O. T. (2021) · Blood · doi:10.1182/blood.2021012112 · Cited by 4
Plant Proteomic Data Acquisition and Data Analyses: Lessons from Spaceflight
Basu, P., Kruse, C. P. S., Luesse, D. R., & Wyatt, S. E. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1677-2_13 · Cited by 2
Preliminary Interpretations of Epigenetic Profiling of Cord Blood in Preeclampsia
Ma, J., Zhan, Z., Li, N., Huang, Y., Li, Y., Liu, L., Shen, Q., Chu, Q., Wang, X., Wu, B., et al. (2022) · Genes · doi:10.3390/genes13050888 · Cited by 2
Computational approaches for hematopoietic stem cells
Raghav, P. K., Banerjee, B., Kumar, R., Raghav, A., Lathwal, A., & Chadha, R. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13222-3.00013-7 · Cited by 2
Transcriptional Activation of Regenerative Hematopoiesis via Vascular Niche SensingPreprint
Itkin, T., Houghton, S., Schreiner, R. P., Lin, Y., Badwe, C. R., Voisin, V., Murison, A., Seyedhassantehrani, N., Kaufmann, K. B., García‐Prat, L., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.27.534417 · Cited by 2
Qi, H., Qiao, M., Liu, Y., Zeng, W., Zhang, L., & Guo, H. (2024) · All Life · doi:10.1080/26895293.2024.2304349 · Cited by 1
Bonadies, N., Göttgens, B., & Calero‐Nieto, F. J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131577 · Cited by 1
“haematopoietic progenitors (HPC7) [42] and human CD34+ peripheral blood cells [43] (Fig 3B and 3C).”
BackgroundCreating cellular diversity through transcription factor competition
Göttgens, B. (2015) · The EMBO Journal · doi:10.15252/embj.201591017 · Cited by 1
ARHGEF4 Regulates an Essential Oncogenic Program in t(12;21)‐Associated Acute Lymphoblastic Leukemia
Virely, C., Gasparoli, L., Mangolini, M., Clesham, K., Inglott, S., Edwards, D., Adams, S. P., Bartram, J. L., Samarasinghe, S., Ancliff, P., et al. (2020) · HemaSphere · doi:10.1097/hs9.0000000000000467 · Cited by 1
“1F, http://links.lww.com/HS/A97), consistent with the increase in cell death observed following ML141 and CASIN treatment (Fig.”
Estevez, B., Borst, S., Jarocha, D., Sudunagunta, V., Gonzalez, M. V., Garifallou, J. P., Hakonarson, H., Gao, P., Tan, K., Liu, P. P., et al. (2020) · bioRxiv · doi:10.1101/2020.08.23.260281
Bone Marrow Microenvironment in Health and Disease
Hoffman, R., & Marcellino, B. K. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11195-x · Cited by 1
Distinct gene regulatory networks govern hematopoietic and leukemia stem cellsPreprint
Zhang, B., Murison, A. J., Varesi, A., Takayama, N., Jin, L., Mbong, N., Schoof, E. M., Xie, S. Z.-J., Mitchell, A., Etchin, J., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.28.614980 · Cited by 1
“…to the sign (i.e., positive or negative) of the regression coefficient, 4) whether the potential regulator is expressed when the region is open, 5) whether the potential regulator’s GE is enriched in stem or non-stem cells, 6) whether the potential regulatory region is more accessible in stem…”
BackgroundSmoking drives an epigenetic memory of aberrant hematopoiesisPreprint
Breeze, C. E., Goodney, G. A., Wang, H., Hubbard, A. K., Lim, J., Machiela, M. J., Hoang, T. T., Richards-Barber, M., Tran, C., Tolentino, M., et al. (2026) · medRxiv · doi:10.64898/2026.05.14.26353250 · Cited by 1
“This likely reflects the scarcity of this primary cell type, which can be harder to obtain than peripheral blood lymphocytes and is often underrepresented in global genomics consortia 33 .”
Characterization of Hemangioma-initiating Stem Cells
Montwill, N. (2017) · Scholarship@Western (Western University)
Elucidating Blood Origin: From Reprogramming to Ontogeny
Gomes, A. M. (2018) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
Nakabayashi, J. (2020) · International Conference on Circuits, Systems, Communications and Computers (CSCC) · doi:10.1109/cscc49995.2020.00025
MAPK Signaling Pathway was Dysregulated in Acute Myeloid Leukemia with RUNX1 MutationsPreprint
he, M., Cai, X., & Zeng, Y. (2021) · Research Square · doi:10.21203/rs.3.rs-502740/v1
Transcriptional circuit dynamics in HSPCs
Tatsumi, G., & Steidl, U. G. (2021) · Blood · doi:10.1182/blood.2021012452
(2020) · International Journal of Biology and Biomedical Engineering · doi:10.46300/91011.2020.14.20
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
“…are remodelled during myeloid progenitor development Genes encoding the heptad TFs form a densely interconnected regulatory circuit in bulk HSPCs (Beck et al., 2013), and chromatin accessibility at heptad gene CREs is sufficient to predict cell identity across blood development (Thoms et al.,…”
BackgroundInfluentialLYL1 is critical for adult hematopoietic stem cell-derived B and T lymphopoiesis
Chiu, S. K., The, J., Saw, J., Boyle, J. A., Curtis, D. J., & Tremblay, C. S. (2026) · Scientific Reports · doi:10.1038/s41598-026-53398-3
FAIRsharing record for: BloodChIP Xtra
FAIRsharing Team, et al. (2024) · FAIRsharing.org · doi:10.25504/fairsharing.5ad8f7
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
