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J Biomed Res
2017 Nov 01;323:215-21. doi: 10.7555/JBR.32.20170056.
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Tcf7l1 promotes transcription of Kruppel-likefactor 4 during Xenopus embryogenesis.
Cao Q
,
Shen Y
,
Zheng W
,
Liu H
,
Liu C
.
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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.
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