The DOI matches its Crossref record; 69 of the 70 references it cites were found in a registry or an index.
Early chromatin unfolding by RUNX1: a molecular explanation for differential requirements during specification versus maintenance of the hematopoietic gene expression program
Open accessAbstract
At the cellular level, development progresses through successive regulatory states, each characterized by their specific gene expression profile. However, the molecular mechanisms regulating first the priming and then maintenance of gene expression within one developmental pathway are essentially unknown. The hematopoietic system represents a powerful experimental model to address these questions and here we have focused on a regulatory circuit playing a central role in myelopoiesis: the transcription factor PU.1, its target gene colony-stimulating-factor 1 receptor (Csf1r), and key upstream regulators such as RUNX1. We find that during ontogeny, chromatin unfolding precedes the establishment of active histone marks and the formation of stable transcription factor complexes at the Pu.1 locus and we show that chromatin remodeling is mediated by the transient binding of RUNX1 to Pu.1 cis-elements. By contrast, chromatin reorganization of Csf1r requires prior expression of PU.1 together with RUNX1 binding. Once the full hematopoietic program is established, stable transcription factor complexes and active chromatin can be maintained without RUNX1. Our experiments therefore demonstrate how individual transcription factors function in a differentiation stage–specific manner to differentially affect the initiation versus maintenance of a developmental program.
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“The best current candidates for this silencing activity include GATA-3 (104, 105), TCF-1 or LEF-1 (37), and especially Runx1 (80, 150–152), probably working in a dose-dependent combination, although the mechanism through which they finally achieve the ability to repress PU.1 has not yet been reported.”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [151]
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Metadata
- Authors
- Hoogenkamp, M., Lichtinger, M., Krysinska, H., Lancrin, C., Clarke, D., Williamson, A., Mazzarella, L., Ingram, R., Jorgensen, H., Fisher, A., Tenen, D. G., Kouskoff, V., Lacaud, G., & Bonifer, C.
- Affiliations
- University of Leeds (GB)
- Cancer Research UK (GB)
- Imperial College London (GB)
- Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London School of Medicine, London, United Kingdom;
- Harvard University (US)
- Cancer Research UK Stem Cell Haematopoiesis Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom;
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2009-07-09
- Volume
- 114
- Issue
- 2
- Pages
- 299-309
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2714206
- OpenAlex
- W2041514505
- Cited by
- 121
- References
- 70
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 7 · 2018: 4 · 2017: 9 · 2016: 9 · 2015: 6 · 2014: 13 · 2013: 11 · 2012: 10
- FWCI
- 5.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- National University of Singapore (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Cancer Research UK
- National Institutes of Health
- Directorate for Biological Sciences
- Medical Research Council
- Biotechnology and Biological Sciences Research Council (BB/F000499/1, BB/E025129/1)
- National Cancer Institute (CA 41456, R01CA041456)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- RUNX1, PU.1, CSF1R, chromatin unfolding, chromatin remodeling, hematopoietic differentiation, myelopoiesis, transcription factor binding, cis-regulatory elements, histone modifications, transcription factor complex, gene expression regulation
- MeSH terms
- Animals, Blood Cells, Cells, Cultured, Chromatin, Gene Expression Regulation, Promoter Regions, Genetic, Protein Binding, RNA, Messenger, Time Factors, DNA Methylation, Core Binding Factor Alpha 2 Subunit, Mice
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