Murato Yasuhito, Yamaguti Mami, Katamura Miho, Cho Ken W Y, Hashimoto Chikara
Department of Biology, Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan.
Int J Dev Biol. 2006;50(5):463-71. doi: 10.1387/ijdb.052106ym.
The Hairy and Enhancer-of-Split (HES) family of transcriptional repressors plays important roles in pattern formation during development throughout the animal kingdom. Generally, HES proteins repress the expression of genes specific for neighboring tissues to maintain the nature of cells expressing HES proteins, resulting in pattern formation. Xhairy2b, a Xenopus HES, establishes the prospective anterior prechordal mesoderm identity in the Spemann-Mangold organizer by both inducing specific genes and repressing the genes specific for neighboring tissues. Here we report that Xhairy2b has two modes of action, each of which corresponds to inductive and repressive functions. We show that the inductive function is independent of direct transcriptional regulation and is exhibited by the C-terminal WRPW tetrapeptide motif alone, although it induces the expression of a wide variety of the organizer genes that Xhairy2b represses. The transcriptional repression by Xhairy2b is responsible for only the repressive function. We propose that the activity of the WRPW motif intrinsically induces the expression of genes specific for the organizer in a rather non-specific manner to ensure the organizer environment. Then, the transcriptional repression selectively down-regulates the expression of some of these genes, resulting in the regionalization of the axial mesoderm. Our study provides new insight into how a region of the vertebrate embryo is demarcated by one dual-functional transcription factor in the early stages of development.
转录抑制因子毛状和分裂增强子（HES）家族在整个动物界发育过程中的模式形成中发挥着重要作用。一般来说，HES蛋白会抑制邻近组织特异性基因的表达，以维持表达HES蛋白的细胞的特性，从而导致模式形成。非洲爪蟾的HES蛋白Xhairy2b，通过诱导特定基因和抑制邻近组织特异性基因，在施佩曼-曼戈尔德组织者中确立了预期的前索前中胚层特征。在此，我们报告Xhairy2b有两种作用模式，每种模式分别对应诱导和抑制功能。我们发现，诱导功能独立于直接转录调控，仅由C端的WRPW四肽基序表现出来，尽管它诱导了多种Xhairy2b所抑制的组织者基因的表达。Xhairy2b的转录抑制作用仅负责其抑制功能。我们提出，WRPW基序的活性以一种相当非特异性的方式内在地诱导组织者特异性基因的表达，以确保组织者环境。然后，转录抑制选择性地下调其中一些基因的表达，导致轴中胚层的区域化。我们的研究为脊椎动物胚胎的一个区域在发育早期如何由一个双功能转录因子划定提供了新的见解。
