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Ventx1.1 作为早期神经基因的直接阻遏物。

Ventx1.1 as a Direct Repressor of Early Neural Gene in .

机构信息

Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University, Gangwon-Do 24252, Korea.

Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 03722, Korea.

出版信息

Mol Cells. 2018 Dec 31;41(12):1061-1071. doi: 10.14348/molcells.2018.0341. Epub 2018 Nov 26.

DOI:10.14348/molcells.2018.0341
PMID:30590909
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6315313/
Abstract

From 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 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 , which is a key early neuro-ectoderm gene, and this Ventx1.1 binding led to repression of transcription. Site-directed mutagenesis of VRE1 and VRE2 within promoter completely abolished the repression caused by Ventx1.1. In addition, we found both the positive and negative regulation of 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 neuro-ectodermal gene during early embryogenesis.

摘要

从胚胎研究来看，BMP4/Smad1 靶向基因回路是外胚层和神经外胚层以及腹侧和背侧中胚层之间的细胞命运指定的关键信号通路。在这种情况下，已经确定了几个 BMP4/Smad1 靶转录因子作为神经外胚层的抑制剂。然而，该途径中的这些直接靶转录因子，包括 GATA1b、Msx1 和 Ventx1.1，都尚未被证明是早期神经外胚层基因表达的直接抑制剂。为了证明 Ventx1.1 是神经外胚层基因的直接抑制剂，我们对 Ventx1.1 进行了全基因组 ChIP-Seq。在这项研究中，我们证明了 Ventx1.1 与关键的早期神经外胚层基因的启动子上的 Ventx1.1 反应顺式作用元件 1 和 2 (VRE1 和 VRE2) 结合，这种 Ventx1.1 结合导致 转录被抑制。在 启动子内 VRE1 和 VRE2 的定点突变完全消除了 Ventx1.1 引起的抑制。此外，我们发现 FoxD5b 和 Xcad2 分别对 启动子活性具有正调控和负调控作用，并且这些作用是通过 VREs 并通过调节 Ventx1.1 水平来实现的。总之，这些结果表明，BMP4/Smad1 靶基因 Ventx1.1 是早期胚胎发生过程中神经外胚层基因 的直接抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45e7/6315313/b2bd054a3982/molce-41-12-1061f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45e7/6315313/dac0c71e4f56/molce-41-12-1061f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45e7/6315313/53ca85d3005e/molce-41-12-1061f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45e7/6315313/0abdf101be49/molce-41-12-1061f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45e7/6315313/6dd342f97903/molce-41-12-1061f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45e7/6315313/b2bd054a3982/molce-41-12-1061f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45e7/6315313/dac0c71e4f56/molce-41-12-1061f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45e7/6315313/53ca85d3005e/molce-41-12-1061f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45e7/6315313/0abdf101be49/molce-41-12-1061f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45e7/6315313/6dd342f97903/molce-41-12-1061f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45e7/6315313/b2bd054a3982/molce-41-12-1061f5.jpg

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