Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biomed Res
2017 Nov 01;323:215-21. doi: 10.7555/JBR.32.20170056.
Show Gene links
Show Anatomy links
Tcf7l1 promotes transcription of Kruppel-likefactor 4 during Xenopus embryogenesis.
Cao Q
,
Shen Y
,
Zheng W
,
Liu H
,
Liu C
.
???displayArticle.abstract???
Kruppel-like factor 4 (Klf4) is a zinc finger transcriptionfactor and plays crucial roles in Xenopus embryogenesis. However, its regulation during embryogenesis is stillunclear. Here, we report that Tcf7l1, a key downstream transducerof the Wnt signaling pathway, could promote Klf4 transcription and stimulate Klf4 promoter activity in early Xenopus embryos. Furthermore, cycloheximide treatmentshowed a direct effect on Klf4 transcriptionfacilitated by Tcf7l1. Moreover, the dominant negative form of Tcf7l1(dnTcf7l1), which lacks N-terminusof the β-catenin binding motif, could still activate Klf4 transcription, suggesting that thisregulation is Wnt/β-catenin independent. Taken together, ourresults demonstrate that Tcf7l1 lies upstream of Klf4 to maintainits expression level during Xenopus embryogenesis.
Fig.1. Klf4 expression is upregulated by Tcf7l1. A: 300 pg of Tcf7l1 mRNAwas injected into 2 or 4-cell stage embryos. Then, the embryos were collected at stage 10.5 for whole-mount in situ hybridization by using Klf4 probe. B: 2 or 4-cell stage embryos were injected with 40 ng ctrlMO or Tcf7l1MO and were collected at stage 28 to test Klf4 expression. C: Quantification of embryos with normal or altered gene expression observed in A and B in two experiments.
Fig.2. Tcf7l1 promotes Klf4 transcription in both whole embryos and animal caps. A: 300 pg of Tcf7l1 mRNA was injected into 4-cell stage embryos, control and injected embryos were collected at stage 10.5. B: For animal cap assay, animal caps were cut at stage 8 and were collected until control embryos reached stage 10.5. C: ctrlMO and Tcf7l1 MO were injected at 40 ng, respectively, and embryos were collected at stage 10.5 for qPCR. Data were presented as mean±SD. Differences between groups were determined by Student's t-test. * indicates P < 0.05. **indicates P < 0.01. qPCR was carried out in three experiments.
Fig.3. Tcf7l1 stimulates Klf4Luc(−2144/ + 70) activity. A and B: 40 pg of Klf4Luc(-2144/ + 70) or PGL3-basic plasmid was injected alone or together with 300 pg Tcf7l1 mRNA, embryos were collected at stage 10.5 for luciferase assay. C: 40 pg Klf4Luc(-2144/ + 70) was co-injected with 20 ng of ctrlMO or Tcf7l1MO, respectively, embryos were collected at stage 10.5 for luciferase assay. Luciferase reporter assay was carried out at 5 (A, B) or 4 (C) independent times. Data were presented as mean±SD. Differences between groups were determined by Student's t-test. *indicates P < 0.05. ** indicates P < 0.01.
Fig.4. Cycloheximide (CHX) treatment shows that Klf4 expression is directly upregulated by Tcf7l1. A: Klf4 expression is shown in response to injection of Tcf7l1 mRNA or dnTcf7l1 mRNA, to treatment with CHX, to injection of Tcf7l1 mRNA or dnTcf7l1 mRNA together with CHX treatment. Embryos were orientated to animal view (An) and vegetal view (Veg). Tcf7l1 mRNA or dnTcf7l1 mRNAwas injected at 300 pg of each embryo. B: Quantification of embryos with normal or altered gene expression observed in three experiments.
Aksoy,
Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells.
2014, Pubmed
Aksoy,
Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells.
2014,
Pubmed
Cao,
Regulation of germ layer formation by pluripotency factors during embryogenesis.
2013,
Pubmed
Cao,
Klf4 is required for germ-layer differentiation and body axis patterning during Xenopus embryogenesis.
2012,
Pubmed
,
Xenbase
Chen,
Krüppel-like factor 4 is transactivated by butyrate in colon cancer cells.
2004,
Pubmed
Cole,
Tcf3 is an integral component of the core regulatory circuitry of embryonic stem cells.
2008,
Pubmed
Dang,
Opposing effects of Krüppel-like factor 4 (gut-enriched Krüppel-like factor) and Krüppel-like factor 5 (intestinal-enriched Krüppel-like factor) on the promoter of the Krüppel-like factor 4 gene.
2002,
Pubmed
Dang,
Expression of the gut-enriched Krüppel-like factor (Krüppel-like factor 4) gene in the human colon cancer cell line RKO is dependent on CDX2.
2001,
Pubmed
Davis-Dusenbery,
down-regulation of Kruppel-like factor-4 (KLF4) by microRNA-143/145 is critical for modulation of vascular smooth muscle cell phenotype by transforming growth factor-beta and bone morphogenetic protein 4.
2011,
Pubmed
Evans,
KLF4 interacts with beta-catenin/TCF4 and blocks p300/CBP recruitment by beta-catenin.
2010,
Pubmed
Fadous-Khalifé,
Krüppel-like factor 4: A new potential biomarker of lung cancer.
2016,
Pubmed
Harland,
In situ hybridization: an improved whole-mount method for Xenopus embryos.
1991,
Pubmed
,
Xenbase
Hikasa,
Regulation of TCF3 by Wnt-dependent phosphorylation during vertebrate axis specification.
2010,
Pubmed
,
Xenbase
Hoffman,
Tcf7l1 prepares epiblast cells in the gastrulating mouse embryo for lineage specification.
2013,
Pubmed
Jiang,
A core Klf circuitry regulates self-renewal of embryonic stem cells.
2008,
Pubmed
Kim,
An extended transcriptional network for pluripotency of embryonic stem cells.
2008,
Pubmed
Kim,
Repressor activity of Headless/Tcf3 is essential for vertebrate head formation.
2000,
Pubmed
King,
Krüppel-like factor 4 (KLF4/GKLF) is a target of bone morphogenetic proteins and transforming growth factor beta 1 in the regulation of vascular smooth muscle cell phenotype.
2003,
Pubmed
Li,
miR-10a restores human mesenchymal stem cell differentiation by repressing KLF4.
2013,
Pubmed
Lin,
A KLF4-miRNA-206 autoregulatory feedback loop can promote or inhibit protein translation depending upon cell context.
2011,
Pubmed
Liu,
Distinct roles for Xenopus Tcf/Lef genes in mediating specific responses to Wnt/beta-catenin signalling in mesoderm development.
2005,
Pubmed
,
Xenbase
Merrill,
Tcf3: a transcriptional regulator of axis induction in the early embryo.
2004,
Pubmed
Molenaar,
XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos.
1996,
Pubmed
,
Xenbase
Shy,
Regulation of Tcf7l1 DNA binding and protein stability as principal mechanisms of Wnt/β-catenin signaling.
2013,
Pubmed
Sorrell,
Tcf7l1 proteins cell autonomously restrict cardiomyocyte and promote endothelial specification in zebrafish.
2013,
Pubmed
Takahashi,
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
2006,
Pubmed
Tian,
Klf4 inhibits tumor growth and metastasis by targeting microRNA-31 in human hepatocellular carcinoma.
2017,
Pubmed
Xu,
MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells.
2009,
Pubmed
Yoon,
Kruppel-like factor 4 mediates p53-dependent G1/S cell cycle arrest in response to DNA damage.
2003,
Pubmed
Zhang,
Novel cross talk of Kruppel-like factor 4 and beta-catenin regulates normal intestinal homeostasis and tumor repression.
2006,
Pubmed
,
Xenbase
Zhao,
RYBP Expression Is Regulated by KLF4 and Sp1 and Is Related to Hepatocellular Carcinoma Prognosis.
2017,
Pubmed
