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A tissue-specific enhancer of the C. elegans nhr-67/tailless gene drives coordinated expression in uterine stem cells and the differentiated anchor cell.
Gene Expression Patterns ( IF 1.2 ) Pub Date : 2018-11-04 , DOI: 10.1016/j.gep.2018.10.003
Shari Bodofsky 1 , Katarina Liberatore 1 , Lauren Pioppo 1 , Dominic Lapadula 1 , Lily Thompson 1 , Susanna Birnbaum 1 , George McClung 1 , Akshara Kartik 1 , Sheila Clever 1 , Bruce Wightman 1
Affiliation  

The nhr-67 nuclear receptor gene of Caenorhabditis elegans encodes the ortholog of the Drosophila tailless and vertebrate Tlx genes. In C. elegans, nhr-67 plays multiple roles in the development of the uterus during L2 and L3 larval stages. Four pre-VU cells are born in the L2 stage and form the precursor complement for the ventral surface of the mature uterus. One of the four pre-VU cells becomes the anchor cell (AC), which exits the cell cycle and differentiates, while the remaining three VU cells serve as stem cells that populate the ventral uterus. The nhr-67 gene functions in the development of both VU cell lineages and AC differentiation. Hypomorphic mutations in nhr-67 identify a 276bp region of the distal promoter that is sufficient to activate nhr-67 expression in pre-VU cells and the AC. The 276bp region includes 8 conserved potential cis-acting sites, including two E boxes and a nuclear receptor binding site. Mutational analysis demonstrates that the two E boxes are required for expression of nhr-67 in uterine precursor cells. The E/daughterless ortholog HLH-2 binds these sites as a homodimer, thus playing a central role in activating nhr-67 expression in the uterine precursors. At least two other binding activities, one of which may be the nhr-25/Ftz-F1 nuclear receptor transcription factor, also contribute to uterine precursor cell expression. The organization of the nhr-67 uterine precursor enhancer is compared to similar conserved enhancers in the egl-43, lag-2, and lin-3 genes, which contain the same HLH-2-binding E boxes and are similarly expressed in both pre-VU cells and the AC. This basic regulatory module allows the coordinated expression of at least four genes. Expression of genes in different cells that must coordinate to form a mature organ is driven by a shared set of promoter elements, which integrate multiple transcription factor inputs.



中文翻译:

秀丽隐杆线虫nhr-67 / tailless基因的组织特异性增强子驱动子宫干细胞和分化的锚细胞中的协同表达。

秀丽隐杆线虫nhr-67核受体基因编码果蝇无尾和脊椎动物Tlx基因的直系同源基因。在秀丽隐杆线虫中nhr-67在L2和L3幼虫阶段的子宫发育中起着多种作用。四个前VU细胞在L2期出生,并形成成熟子宫腹面的前体补体。四个前VU细胞之一成为锚定细胞(AC),它退出细胞周期并分化,而其余三个VU细胞则充当了腹侧子宫的干细胞。该NHR-67基因在VU细胞谱系和AC分化的发育中起作用。nhr -67中的亚型突变确定了远端启动子的276bp区域,足以激活前VU细胞和AC中nhr-67的表达。276bp的区域包括8个保守的潜在顺式作用位点,包括两个E盒和一个核受体结合位点。突变分析表明,在子宫前体细胞中表达nhr-67需要两个E盒。的E / daughterless直系同源HLH-2结合这些站点作为同二聚体,由此在激活中心作用NHR-67在子宫前体的表达。至少还有两个其他绑定活动,其中之一可能是nhr-25 / Ftz-F1核受体转录因子,也有助于子宫前体细胞表达。将nhr-67子宫前体增强子的组织与egl-43,lag-2lin-3基因中类似的保守增强子进行比较,它们包含相同的HLH-2结合E盒,并且在两个前体中均类似表达-VU电池和AC。该基本调节模块允许至少四个基因的协同表达。基因在必须协调形成成熟器官的不同细胞中的表达受一组共享多个转录因子输入的启动子元件驱动。

更新日期:2018-11-04
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