Ventx1.1 as a Direct Repressor of Early Neural Gene zic3 in Xenopus laevis
Zobia Umair1, Shiv Kumar1, Daniel H. Kim3, Khezina Rafiq1, Vijay Kumar1, SungChan Kim1, Jae-Bong Park1, Jae-Yong Lee1, Unjoo Lee2,*, and Jaebong Kim1,*
1Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, 2Department of Electrical Engineering, Hallym University, Gangwon-Do 24252, Korea, 3Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 03722, Korea
*Correspondence: (JBK); (UJL)
Received August 13, 2018; Accepted September 18, 2018.; Published online November 26, 2018.
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From Xenopus embryo studies, the BMP4/Smad1-targeted gene circuit is a key signaling pathway for specifying the cell fate between the ectoderm and neuro-ectoderm as well as the ventral and dorsal mesoderm. In this context, several BMP4/Smad1 target transcriptional factors have been identified as repressors of the neuro-ectoderm. However, none of these direct target transcription factors in this pathway, including GATA1b, Msx1 and Ventx1.1 have yet been proven as direct repressors of early neuro-ectodermal gene expression. In order to demonstrate that Ventx1.1 is a direct repressor of neuro-ectoderm genes, a genome-wide Xenopus ChIP-Seq of Ventx1.1 was performed. In this study, we demonstrated that Ventx1.1 bound to the Ventx1.1 response cis-acting element 1 and 2 (VRE1 and VRE2) on the promoter for zic3, which is a key early neuro-ectoderm gene, and this Ventx1.1 binding led to repression of zic3 transcription. Site-directed mutagenesis of VRE1 and VRE2 within zic3 promoter completely abolished the repression caused by Ventx1.1. In addition, we found both the positive and negative regulation of zic3 promoter activity by FoxD5b and Xcad2, respectively, and that these occur through the VREs and via modulation of Ventx1.1 levels. Taken together, the results demonstrate that the BMP4/Smad1 target gene, Ventx1.1, is a direct repressor of neuroectodermal gene zic3 during early Xenopus embryogenesis.
neurogenesis, transcriptional regulation, Ventx1.1, Xenopus, zic3

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30 November 2018 Volume 41,
Number 11, pp. 933~992

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