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Publication : An Evolutionarily Conserved Mesodermal Enhancer in Vertebrate Zic3.

First Author  Odaka YS Year  2018
Journal  Sci Rep Volume  8
Issue  1 Pages  14954
PubMed ID  30297839 Mgi Jnum  J:310742
Mgi Id  MGI:6763839 Doi  10.1038/s41598-018-33235-y
Citation  Odaka YS, et al. (2018) An Evolutionarily Conserved Mesodermal Enhancer in Vertebrate Zic3. Sci Rep 8(1):14954
abstractText  Zic3 encodes a zinc finger protein essential for the development of meso-ectodermal tissues. In mammals, Zic3 has important roles in the development of neural tube, axial skeletons, left-right body axis, and in maintaining pluripotency of ES cells. Here we characterized cis-regulatory elements required for Zic3 expression. Enhancer activities of human-chicken-conserved noncoding sequences around Zic1 and Zic3 were screened using chick whole-embryo electroporation. We identified enhancers for meso-ectodermal tissues. Among them, a mesodermal enhancer (Zic3-ME) in distant 3' flanking showed robust enhancement of reporter gene expression in the mesodermal tissue of chicken and mouse embryos, and was required for mesodermal Zic3 expression in mice. Zic3-ME minimal core region is included in the DNase hypersensitive region of ES cells, mesoderm, and neural progenitors, and was bound by T (Brachyury), Eomes, Lef1, Nanog, Oct4, and Zic2. Zic3-ME is derived from an ancestral sequence shared with a sequence encoding a mitochondrial enzyme. These results indicate that Zic3-ME is an integrated cis-regulatory element essential for the proper expression of Zic3 in vertebrates, serving as a hub for a gene regulatory network including Zic3.
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