Repression of Nanog Gene Transcription by Tcf3 Limits Embryonic Stem Cell Self-renewal

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2006 Aug 9

PMID 16894029

Citations 161

Authors

Laura Pereira

Fei Yi

Bradley J Merrill

Affiliations

Soon will be listed here.

Abstract

The dual function of stem cells requires them not only to form new stem cells through self-renewal but also to form lineage-committed cells through differentiation. Embryonic stem cells (ESC), which are derived from the blastocyst inner cell mass, retain properties of self-renewal and the potential for lineage commitment. To balance self-renewal and differentiation, ESC must carefully control the levels of several transcription factors, including Nanog, Sox2, and Oct4. While molecular mechanisms promoting transcription of these genes have been described, mechanisms preventing excessive levels in self-renewing ESC remain unknown. By examining the function of the TCF family of transcription factors in ESC, we have found that Tcf3 is necessary to limit the steady-state levels of Nanog mRNA, protein, and promoter activity in self-renewing ESC. Chromatin immunoprecipitation and promoter reporter assays showed that Tcf3 bound to a promoter regulatory region of the Nanog gene and repressed its transcriptional activity in ESC through a Groucho interaction domain-dependent process. The absence of Tcf3 caused delayed differentiation of ESC in vitro as elevated Nanog levels persisted through 5 days of embryoid body formation. These new data support a model wherein Tcf3-mediated control of Nanog levels allows stem cells to balance the creation of lineage-committed and undifferentiated cells.

Citing Articles

MACC1 revisited - an in-depth review of a master of metastasis.

Schope P, Torke S, Kobelt D, Kortum B, Treese C, Dumbani M Biomark Res. 2024; 12(1):146.

PMID: 39580452 PMC: 11585957. DOI: 10.1186/s40364-024-00689-4.

SRRM2 splicing factor modulates cell fate in early development.

Carvalho S, Zea-Redondo L, Tang T, Stachel-Braum P, Miller D, Caldas P Biol Open. 2024; 13(4).

PMID: 38656788 PMC: 11070786. DOI: 10.1242/bio.060415.

RNF2 regulates Wnt/ß-catenin signaling via TCF7L1 destabilization.

Koo Y, Han W, Keum B, Lutz L, Yun S, Kim G Sci Rep. 2023; 13(1):19750.

PMID: 37957244 PMC: 10643375. DOI: 10.1038/s41598-023-47111-x.

miR-133a-3p and miR-145-5p co-promote goat hair follicle stem cell differentiation by regulating NANOG and SOX9 expression.

Wang J, Wu X, Zhang L, Wang Q, Sun X, Ji D Anim Biosci. 2023; 37(4):609-621.

PMID: 37946416 PMC: 10915213. DOI: 10.5713/ab.23.0348.

β-CATENIN stabilizes HIF2 through lncRNA and inhibits intravenous immunoglobulin immunotherapy.

Nakagawa C, Kadlera Nagaraj M, Hernandez J, Uthay Kumar D, Shukla V, Machida R Front Immunol. 2023; 14:1204907.

PMID: 37744383 PMC: 10516572. DOI: 10.3389/fimmu.2023.1204907.

References

Niwa H, Miyazaki J, Smith A . Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet. 2000; 24(4):372-6. DOI: 10.1038/74199. View

Reya T, Duncan A, Ailles L, Domen J, Scherer D, Willert K . A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature. 2003; 423(6938):409-14. DOI: 10.1038/nature01593. View

Tumbar T, Guasch G, Greco V, Blanpain C, Lowry W, Rendl M . Defining the epithelial stem cell niche in skin. Science. 2003; 303(5656):359-63. PMC: 2405920. DOI: 10.1126/science.1092436. View

Lee H, Kleber M, Hari L, Brault V, Suter U, Taketo M . Instructive role of Wnt/beta-catenin in sensory fate specification in neural crest stem cells. Science. 2004; 303(5660):1020-3. DOI: 10.1126/science.1091611. View

Hart A, Hartley L, Ibrahim M, Robb L . Identification, cloning and expression analysis of the pluripotency promoting Nanog genes in mouse and human. Dev Dyn. 2004; 230(1):187-98. DOI: 10.1002/dvdy.20034. View

Otero J, Fu W, Kan L, Cuadra A, Kessler J . Beta-catenin signaling is required for neural differentiation of embryonic stem cells. Development. 2004; 131(15):3545-57. DOI: 10.1242/dev.01218. View

Stevens L . The development of transplantable teratocarcinomas from intratesticular grafts of pre- and postimplantation mouse embryos. Dev Biol. 1970; 21(3):364-82. DOI: 10.1016/0012-1606(70)90130-2. View

Mintz B, Illmensee K . Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci U S A. 1975; 72(9):3585-9. PMC: 433040. DOI: 10.1073/pnas.72.9.3585. View

Evans M, Kaufman M . Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981; 292(5819):154-6. DOI: 10.1038/292154a0. View

10.

Martin G . Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A. 1981; 78(12):7634-8. PMC: 349323. DOI: 10.1073/pnas.78.12.7634. View

11.

Williams R, Hilton D, Pease S, Willson T, Stewart C, Gearing D . Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature. 1988; 336(6200):684-7. DOI: 10.1038/336684a0. View

12.

Zhou P, Byrne C, Jacobs J, Fuchs E . Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate. Genes Dev. 1995; 9(6):700-13. DOI: 10.1101/gad.9.6.700. View

13.

Yuan H, Corbi N, Basilico C, Dailey L . Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3. Genes Dev. 1995; 9(21):2635-45. DOI: 10.1101/gad.9.21.2635. View

14.

Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V . XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell. 1996; 86(3):391-9. DOI: 10.1016/s0092-8674(00)80112-9. View

15.

van de Wetering M, Cavallo R, Dooijes D, van Beest M, van Es J, Loureiro J . Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell. 1997; 88(6):789-99. DOI: 10.1016/s0092-8674(00)81925-x. View

16.

Brannon M, Gomperts M, Sumoy L, Moon R, Kimelman D . A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus. Genes Dev. 1997; 11(18):2359-70. PMC: 316518. DOI: 10.1101/gad.11.18.2359. View

17.

Botquin V, Hess H, Fuhrmann G, Anastassiadis C, Gross M, Vriend G . New POU dimer configuration mediates antagonistic control of an osteopontin preimplantation enhancer by Oct-4 and Sox-2. Genes Dev. 1998; 12(13):2073-90. PMC: 316977. DOI: 10.1101/gad.12.13.2073. View

18.

Cavallo R, Cox R, Moline M, Roose J, Polevoy G, Clevers H . Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature. 1998; 395(6702):604-8. DOI: 10.1038/26982. View

19.

Roose J, Molenaar M, Peterson J, Hurenkamp J, Brantjes H, Moerer P . The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature. 1998; 395(6702):608-12. DOI: 10.1038/26989. View

20.

Nichols J, Zevnik B, Anastassiadis K, Niwa H, Chambers I, Scholer H . Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell. 1998; 95(3):379-91. DOI: 10.1016/s0092-8674(00)81769-9. View