A SINE-derived element constitutes a unique modular enhancer for mammalian diencephalic Fgf8.
A SINE-derived element constitutes a unique modular enhancer for mammalian diencephalic Fgf8.
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DOI：
10.1371/journal.pone.0043785
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Okada N
中科院分区：
文献类型：
--
作者：
Nakanishi A;Kobayashi N;Suzuki-Hirano A;Nishihara H;Sasaki T;Hirakawa M;Sumiyama K;Shimogori T;Okada N
转座元件，包括短散布重复元件（西内斯），包含近一半的哺乳动物基因组。此外，它们还是保守非编码元件（conserved non-coding elements，CNEs）的重要来源，在调节发育相关基因的增强和沉默等方面发挥重要的功能作用，为物种间形态和生理特征的多样性服务。我们以前报道了一个新的SINE家族，AmnSINE 1，作为西印度群岛特有的CNE的一部分。一个AmnSINE 1位点，命名为AS 071，在发育中的小鼠间脑中显示出增强子特性。事实上，AS 071似乎重现间脑成纤维细胞生长因子8（Fgf 8）的表达。在这里，我们建立了三个独立的系的AS 071转基因小鼠，并进行了详细的表达谱的AS 071增强lacZ与Fgf 8在整个胚胎阶段的比较。我们证明，AS 071是一个远端增强子，指导Fgf 8在发育中的间脑表达。此外，用编码部分缺失的AS 071序列的构建体进行的增强子测定揭示了一种独特的模块化组织，其中AS 071包含至少三个功能不同的子元件，这些子元件协同指导三个间脑结构域（即间脑的背侧中线和侧壁以及下丘脑的腹侧中线）中的增强子活性。有趣的是，发现AmnSINE 1衍生的子元件指定增强子活性至下丘脑的腹侧中线。据我们所知，这是第一次发现一个增强子元件，可以分为相应的子元件，确定区域特异性和/或核心增强活性。这些结果加强了我们对逆转录酶衍生的顺式调控元件的进化的理解，以及为未来研究增强子的结构域特异性的分子机制奠定了基础。
Transposable elements, including short interspersed repetitive elements (SINEs), comprise nearly half the mammalian genome. Moreover, they are a major source of conserved non-coding elements (CNEs), which play important functional roles in regulating development-related genes, such as enhancing and silencing, serving for the diversification of morphological and physiological features among species. We previously reported a novel SINE family, AmnSINE1, as part of mammalian-specific CNEs. One AmnSINE1 locus, named AS071, showed an enhancer property in the developing mouse diencephalon. Indeed, AS071 appears to recapitulate the expression of diencephalic fibroblast growth factor 8 (Fgf8). Here we established three independent lines of AS071-transgenic mice and performed detailed expression profiling of AS071-enhanced lacZ in comparison with that of Fgf8 across embryonic stages. We demonstrate that AS071 is a distal enhancer that directs Fgf8 expression in the developing diencephalon. Furthermore, enhancer assays with constructs encoding partially deleted AS071 sequence revealed a unique modular organization in which AS071 contains at least three functionally distinct sub-elements that cooperatively direct the enhancer activity in three diencephalic domains, namely the dorsal midline and the lateral wall of the diencephalon, and the ventral midline of the hypothalamus. Interestingly, the AmnSINE1-derived sub-element was found to specify the enhancer activity to the ventral midline of the hypothalamus. To our knowledge, this is the first discovery of an enhancer element that could be separated into respective sub-elements that determine regional specificity and/or the core enhancing activity. These results potentiate our understanding of the evolution of retroposon-derived cis-regulatory elements as well as the basis for future studies of the molecular mechanism underlying the determination of domain-specificity of an enhancer.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
2.7
作者：
Inoue, Fumitaka;Parvin, Mst. Shahnaj;Yamasu, Kyo
通讯作者：
Yamasu, Kyo
影响因子：
--
作者：
Echevarria, D;Belo, JA;Martinez, S
通讯作者：
Martinez, S
影响因子：
5.1
作者：
Fukada, Y;Okano, T
通讯作者：
Okano, T
DOI：
10.1111/j.1749-6632.2009.04435.x
发表时间：
2009-01-01
期刊：
TRENDS IN COMPARATIVE ENDOCRINOLOGY AND NEUROBIOLOGY
影响因子：
--
作者：
Falcon, Jack;Besseau, Laurence;Boeuf, Gilles
通讯作者：
Boeuf, Gilles