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Biochim Biophys Acta Gene Regul Mech. 2017 Oct;1860(10):1103-1116. doi: 10.1016/j.bbagrm.2017.09.001. Epub 2017 Sep 6.

Transcriptional factors Eaf1/2 inhibit endoderm and mesoderm formation via suppressing TGF-β signaling.

Author information

1
College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, 430070, China; Key Laboratory of Biodiversity and Conservation of Aquatic Organisms, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China. Electronic address: ichliu@mail.hzau.edu.cn.
2
College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, 430070, China.
3
College of informatics, Agricultural Bioinformatics Key Laboratory of Hubei Province, Huazhong Agricultural University, Wuhan, 430070, China.
4
Key Laboratory of Biodiversity and Conservation of Aquatic Organisms, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.

Abstract

Eaf family genes act in multiple cellular responses such as tumor suppression and embryonic development. In our previous work, Eaf1/2 was found to modulate convergence and extension (C&E) movements and pattern the embryonic anterior-posterior axis during zebrafish embryogenesis. Here, we found that loss-of-function of eaf1/2 caused expanded mesoderm and endoderm in zebrafish embryos and led to the recovery of endoderm specification in TGF-β factor-mzoeptz257 mutants, while gain-of-function of eaf1/2 induced reduced mesoderm and endoderm. Analyses of gene expression profiles in Eaf deleted or over-expressed mammalian cells indicated that the roles of Eaf1 and Eaf2 in inhibiting TGF-β signals were conserved from fish to mammals. By taking advantages of TGF-β reporters, eaf1/2-fused engrailed proteins, and P53M214K mutant, we revealed that Eaf1 and Eaf2 might suppress TGF-β transduction by synergistically inhibiting none-P53 and P53-required TGF-β signaling. Furthermore, Eaf1/2 might co-localize and interact with TGF-β transcriptional factors in the transcriptional complex as repressors to target and suppress TGF-β signaling activity. Our study unveiled a previously unrecognized link of Eaf1/2 genes with TGF-β and P53 in vertebrates and demonstrated a conservation of TGF-β suppression activity for Eaf1/2 family genes from fish to mammals, which might shed some light on the molecular mechanistic basis of Eaf1 and Eaf2 in tumor suppression.

KEYWORDS:

Eaf1/2; Endoderm; Mesoderm; P53; TGF-β

PMID:
28887217
DOI:
10.1016/j.bbagrm.2017.09.001
[Indexed for MEDLINE]

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