Cited by 83Pluripotent Stem Cells ResearchDevelopmental Biology and Gene RegulationEpigenetics and DNA Methylation

Dual Functions of T-Box 3 (Tbx3) in the Control of Self-renewal and Extraembryonic Endoderm Differentiation in Mouse Embryonic Stem Cells

Open access
Lu, Rui, Yang, Acong, Jin, Ying·2011·Journal of Biological Chemistry

Abstract

Embryonic stem cells (ESCs) possess the capacity to proliferate indefinitely in an undifferentiated state and to differentiate into various cell types in an organism. However, the critical question of how self-renewal and differentiation are precisely regulated in ESCs is not entirely understood at present. Here, we report the essential role of Tbx3, a pluripotency-related transcription factor of the T-box gene family, for both the maintenance of self-renewal of mouse ESCs and for their differentiation into extraembryonic endoderm (ExEn). We show that Tbx3 is highly expressed in ExEn cells in addition to undifferentiated ESCs. Knockdown of Tbx3 expression using tetracycline-regulated Tbx3 siRNA resulted in the attenuation of ESC self-renewal ability and aberrant differentiation processes, including reduced ExEn differentiation but enhanced ectoderm and trophectoderm differentiation. Conversely, inducible forced expression of Tbx3 triggered ExEn lineage commitment. Mechanistically, Tbx3 directly activated the expression of Gata6, an essential regulator of ExEn. Interestingly, Tbx3 modulated H3K27me3 modification and the association of the PRC2 complex with the promoter region of Gata6. Taken together, the results of this study revealed a previously unappreciated role of a pluripotency factor in ExEn differentiation. Additionally, our data reveal that Tbx3 may function through direct binding and epigenetic modification of histones on the Gata6 promoter to maintain the ExEn differentiation potential of ESCs.

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  • TBX3 has been shown to directly promote the expression of target genes by binding to specific DNA sequences within those genes.

    “TBX3 has been shown to directly promote the expression of target genes by binding to specific DNA sequences within those genes.”
  • Tbx3 directly activates Gata6 expression via its DNA binding activity.

    “Tbx3 directly activates Gata6 expression via its DNA binding activity. TBX3 has been shown to directly bind to the promoter of the Gata6 gene, a key regulatory protein of primitive endoderm differentiation, activating the expression of this gene 78.”
  • TBX3 is critically involved in pluripotency maintenance and lineage-specific exit from the pluripotency circuitry in mouse embryonic stem cells.

    “Finally, TBX3 is not only critically involved in pluripotency maintenance but also in lineage-specific exit from the pluripotency circuitry in mouse embryonic stem cells [11–17].”

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Authors
Lu, R., Yang, A., & Jin, Y.
Affiliations
Shanghai Jiao Tong University (CN)
Corresponding author
Jin, Ying
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2011-03
Volume
286
Issue
10
Pages
8425-8436
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1979308978
Cited by
80
References
38
Citations by year
2026: 3 · 2025: 2 · 2024: 6 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 2 · 2019: 5 · 2018: 5 · 2017: 5 · 2016: 5 · 2015: 6 · 2014: 9 · 2013: 10 · 2012: 8
FWCI
2.61
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
TBX3, mouse embryonic stem cells, self-renewal, GATA6, polycomb repressive complex 2, H3K27me3, histone modifications, pluripotency transcription factors, trophectoderm differentiation, ectoderm differentiation, lineage commitment, epigenetic regulation
MeSH terms
Animals, Cell Differentiation, Cell Line, Endoderm, Histones, Promoter Regions, Genetic, Protein Processing, Post-Translational, Gene Expression Regulation, Developmental, Cell Lineage, T-Box Domain Proteins, Epigenesis, Genetic, GATA6 Transcription Factor, Mice, Embryonic Stem Cells, Gene Knockdown Techniques

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