Regulation of Lymphoid versus Myeloid Fate 'choice' by the Transcription Factor Mef2c
Abstract
Despite advances in the identification of lymphoid-restricted progenitor cells, the transcription factors essential for their generation remain to be identified. Here we describe an unexpected function for the myeloid oncogene product Mef2c in lymphoid development. Mef2c deficiency was associated with profound defects in the production of B cells, T cells, natural killer cells and common lymphoid progenitor cells and an enhanced myeloid output. In multipotent progenitors, Mef2c was required for the proper expression of several key lymphoid regulators and restriction of the myeloid fate. Our studies also show that Mef2c was a critical transcriptional target of the transcription factor PU.1 during lymphopoiesis. Thus, Mef2c is a crucial component of the transcriptional network that regulates cell fate 'choice' in multipotent progenitors.
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PU.1 occupancy at MEF2C regulatory regions has been reported.
“Additionally, PU.1 occupancy at MEF2C regulatory regions has been reported [64], and MEF2C in turn regulates genes involved in synaptic support and anti‐inflammatory responses [45].”
From Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease (2026) · cites this paper as [64]
PU.1 functions as a pioneer transcriptional factor that establishes enhancer accessibility in myeloid lineage cells and directly induces expression of other transcriptional factors, such as IRF8 and MEF2C.
“Especially, PU.1 functions as a pioneer transcriptional factor that establishes enhancer accessibility in myeloid lineage cells and directly induces expression of other transcriptional factors (e.g., IRF8, MEF2C) [29, 64, 69, 70].”
From Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease (2026) · cites this paper as [64]
Cites
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“Additionally, microarray expression profiling has identified Mef2c as a gene activated by human oncogenes derived from the Ml1l-Mllt3 and Nup98-Hox10A translocations, which indicates that Mef2c is a critical mediator of the self-renewal of cancer progenitor cells with those translocation”
BackgroundDynamic regulation of PU.1 expression in multipotent hematopoietic progenitors
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Dnmt3a is essential for hematopoietic stem cell differentiation
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“1 deficiency, is broadly similar to that observed in mice lacking E2A (26), Mef2c (28), Ikaros (31, 62), and Myb (27), factors also required for the priming of lymphoid lineage genes in LSK cells.”
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Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease
Kim, B., Wang, S. S., Kim, J. R., & Kim, J. (2026) · BioEssays · doi:10.1002/bies.70186
“Additionally, PU.1 occupancy at MEF2C regulatory regions has been reported [64], and MEF2C in turn regulates genes involved in synaptic support and anti-inflammatory responses [45].”
- Authors
- Stehling-Sun, S., Dade, J., Nutt, S. L., DeKoter, R. P., & Camargo, F. D.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- University of Cincinnati (US)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Corresponding author
- Camargo, Fernando D
- Venue
- Nature Immunology
- Published
- 2009-01-25
- Volume
- 10
- Issue
- 3
- Pages
- 289-296
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2021539006
- Cited by
- 125
- References
- 5
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 9 · 2023: 7 · 2022: 7 · 2021: 9 · 2020: 4 · 2019: 10 · 2018: 8 · 2017: 5 · 2016: 6 · 2015: 8 · 2014: 7 · 2013: 4 · 2012: 12
- FWCI
- 7.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI052175, AI052175)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- MEF2C, lymphoid development, myeloid differentiation, cell fate determination, multipotent progenitors, B cells, T cells, natural killer cells, PU.1, transcriptional regulation, lymphocyte development, transcription factors
- MeSH terms
- Proto-Oncogene Protein Spi-1, Animals, Flow Cytometry, Mice, Inbred C57BL, Proto-Oncogene Proteins, Trans-Activators, Myogenic Regulatory Factors, Mice, Knockout, Hematopoietic Stem Cell Transplantation, Gene Expression Regulation, Developmental, Gene Expression Profiling, Lymphopoiesis, Mice, Lymphoid Progenitor Cells, MEF2 Transcription Factors
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