The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation
Open accessAbstract
We describe a pathway by which the master transcription factor PU.1 regulates human monocyte/macrophage differentiation. This includes miR-424 and the transcriptional factor NFI-A. We show that PU.1 and these two components are interlinked in a finely tuned temporal and regulatory circuitry: PU.1 activates the transcription of miR-424, and this up-regulation is involved in stimulating monocyte differentiation through miR-424-dependent translational repression of NFI-A. In turn, the decrease in NFI-A levels is important for the activation of differentiation-specific genes such as M-CSFr . In line with these data, both RNAi against NFI-A and ectopic expression of miR-424 in precursor cells enhance monocytic differentiation, whereas the ectopic expression of NFI-A has an opposite effect. The interplay among these three components was demonstrated in myeloid cell lines as well as in human CD34+ differentiation. These data point to the important role of miR-424 and NFI-A in controlling the monocyte/macrophage differentiation program.
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PU.1 upregulates miR-424, which suppresses the transcriptional factor NFI-A, subsequently stimulating monocyte differentiation through differentiation-specific genes such as M-CSFr.
“PU.1 upregulates miR-424, which suppresses the transcriptional factor NFI-A, subsequently stimulating monocyte differentiation through differentiation-specific genes such as M-CSFr [187].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [187]
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- Authors
- Rosa, A., Ballarino, M., Sorrentino, A., Sthandier, O., De Angelis, F. G., Marchioni, M., Masella, B., Guarini, A., Fatica, A., Peschle, C., & Bozzoni, I.
- Affiliations
- Institut Pasteur (FR)
- Istituto Superiore di Sanità (IT)
- *Institute Pasteur Cenci-Bolognetti, Department of Genetics and Molecular Biology,
- Institute of Molecular Biology and Pathology (IT)
- Sapienza University of Rome (IT)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-12-11
- Volume
- 104
- Issue
- 50
- Pages
- 19849-19854
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2148386
- OpenAlex
- W2054067310
- Cited by
- 285
- References
- 2
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 11 · 2023: 9 · 2022: 8 · 2021: 13 · 2020: 14 · 2019: 14 · 2018: 7 · 2017: 17 · 2016: 19 · 2015: 20 · 2014: 18 · 2013: 31 · 2012: 22
- FWCI
- 6.49
- 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)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- European Commission (LSHG-CT-2006-037900)
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- PU.1, miR-424, monocyte differentiation, macrophage differentiation, microRNA regulation, protein synthesis inhibition, transcriptional regulation, M-CSF receptor, myeloid cells, CD34+ cells, hematopoiesis
- MeSH terms
- Proto-Oncogene Protein Spi-1, Base Sequence, Cell Differentiation, Cells, Cultured, Hematopoiesis, Humans, Macrophages, Monocytes, Protein Binding, Proto-Oncogene Proteins, Trans-Activators, Up-Regulation, MicroRNAs, NFI Transcription Factors
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