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阈值依赖性转录识别是干细胞稳态的基础。

Threshold-dependent transcriptional discrimination underlies stem cell homeostasis.

作者信息

Perales Mariano, Rodriguez Kevin, Snipes Stephen, Yadav Ram Kishor, Diaz-Mendoza Mercedes, Reddy G Venugopala

机构信息

Department of Botany and Plant Sciences, Institute of Integrative Genome Biology, Center for Plant Cell Biology, University of California, Riverside, CA 92521.

Department of Botany and Plant Sciences, Institute of Integrative Genome Biology, Center for Plant Cell Biology, University of California, Riverside, CA 92521

出版信息

Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):E6298-E6306. doi: 10.1073/pnas.1607669113. Epub 2016 Sep 26.

DOI:10.1073/pnas.1607669113
PMID:27671653
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5068294/
Abstract

Transcriptional mechanisms that underlie the dose-dependent regulation of gene expression in animal development have been studied extensively. However, the mechanisms of dose-dependent transcriptional regulation in plant development have not been understood. In Arabidopsis shoot apical meristems, WUSCHEL (WUS), a stem cell-promoting transcription factor, accumulates at a higher level in the rib meristem and at a lower level in the central zone where it activates its own negative regulator, CLAVATA3 (CLV3). How WUS regulates CLV3 levels has not been understood. Here we show that WUS binds a group of cis-elements, cis- regulatory module, in the CLV3-regulatory region, with different affinities and conformations, consisting of monomers at lower concentration and as dimers at a higher level. By deleting cis elements, manipulating the WUS-binding affinity and the homodimerization threshold of cis elements, and manipulating WUS levels, we show that the same cis elements mediate both the activation and repression of CLV3 at lower and higher WUS levels, respectively. The concentration-dependent transcriptional discrimination provides a mechanistic framework to explain the regulation of CLV3 levels that is critical for stem cell homeostasis.

摘要

动物发育过程中基因表达剂量依赖性调控的转录机制已得到广泛研究。然而,植物发育过程中剂量依赖性转录调控的机制尚不清楚。在拟南芥茎尖分生组织中,促进干细胞的转录因子WUSCHEL(WUS)在肋状分生组织中积累水平较高,而在中央区域积累水平较低,在中央区域它激活自身的负调控因子CLAVATA3(CLV3)。WUS如何调节CLV3水平尚不清楚。在这里,我们表明WUS以不同的亲和力和构象结合CLV3调控区域中的一组顺式元件,即顺式调控模块,在较低浓度下以单体形式存在,在较高水平下以二聚体形式存在。通过删除顺式元件、操纵WUS结合亲和力和顺式元件的同源二聚化阈值以及操纵WUS水平,我们表明相同的顺式元件分别在较低和较高WUS水平下介导CLV3的激活和抑制。浓度依赖性转录识别提供了一个机制框架来解释对干细胞稳态至关重要的CLV3水平的调控。

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本文引用的文献

1
DNA-dependent homodimerization, sub-cellular partitioning, and protein destabilization control WUSCHEL levels and spatial patterning.依赖DNA的同源二聚化、亚细胞定位和蛋白质稳定性调控决定了WUSCHEL蛋白的水平和空间模式。
Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):E6307-E6315. doi: 10.1073/pnas.1607673113. Epub 2016 Sep 26.
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Stem Cell Regulation by Arabidopsis WOX Genes.拟南芥 WOX 基因对干细胞的调控
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Control of plant stem cell function by conserved interacting transcriptional regulators.通过保守的相互作用转录调节因子控制植物干细胞功能。
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A mechanistic framework for noncell autonomous stem cell induction in Arabidopsis.拟南芥中非细胞自主性干细胞诱导的机制框架。
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Plant stem cell maintenance involves direct transcriptional repression of differentiation program.植物干细胞的维持涉及分化程序的直接转录抑制。
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WUSCHEL protein movement mediates stem cell homeostasis in the Arabidopsis shoot apex.WUSCHEL 蛋白运动介导拟南芥茎尖干细胞的内稳态。
Genes Dev. 2011 Oct 1;25(19):2025-30. doi: 10.1101/gad.17258511.
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LOST MERISTEMS genes regulate cell differentiation of central zone descendants in Arabidopsis shoot meristems.LOST 分生组织基因调控拟南芥茎分生组织中央区后代的细胞分化。
Plant J. 2010 Nov;64(4):668-78. doi: 10.1111/j.1365-313X.2010.04359.x. Epub 2010 Oct 8.
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WUSCHEL mediates stem cell homeostasis by regulating stem cell number and patterns of cell division and differentiation of stem cell progenitors.WUSCHEL 通过调节干细胞数量以及干细胞祖细胞的细胞分裂和分化模式来介导干细胞的自我更新。
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Hormonal control of the shoot stem-cell niche.激素对茎干细胞龛的调控。
Nature. 2010 Jun 24;465(7301):1089-92. doi: 10.1038/nature09126.