ELT-2 is the predominant transcription factor controlling differentiation and function of the C. elegans intestine, from embryo to adult.
ELT-2 is the predominant transcription factor controlling differentiation and function of the C. elegans intestine, from embryo to adult.
复制标题
DOI：
10.1016/j.ydbio.2008.11.034
复制
发表时间：
2009-03-15
影响因子：
2.7
通讯作者：
Kalb, John M.
中科院分区：
文献类型：
--
作者：
McGhee, James D.;Fukushige, Tetsunari;Krause, Michael W.;Minnema, Stephanie E.;Goszczynski, Barbara;Gaudet, Jeb;Kohara, Yuji;Bossinger, Olaf;Zhao, Yongjun;Khattra, Jaswinder;Hirst, Martin;Jones, Steven J. M.;Marra, Marco A.;Ruzanov, Peter;Warner, Adam;Zapf, Richard;Moerman, Donald G.;Kalb, John M.
关键词：
从线虫FAC分选的胚胎肠道细胞(8E-16E细胞期)、总胚胎和纯化的卵母细胞制备的SAGE文库开始，利用NextDB原位杂交数据库，我们定义了合子基因组高表达的基因集，并在胚胎肠道或新孵化的幼虫的肠道中唯一或优先表达；我们以前定义了一组类似表达的成人肠道基因。我们表明，扩展的TGATAA类序列基本上是所有阶段表达的肠道基因共同的顺式作用调控基序的唯一候选者。这个序列是一个很强的ELT-2结合位点，与迄今为止实验分析的每个肠道基因的表达重要的GATA样位点的序列相匹配。我们发现，在这三组高表达的肠道特异/肠道丰富的基因中，大多数对ELT-2在胚胎中的异位表达有强烈的反应。通过对ELT-2(+)幼虫的ELT-2(空)幼虫进行流式分选，然后制备Solexa/Illumina-SAGE文库，我们发现这些基因中的大多数也对ELT-2的功能丧失有强烈的反应。为了测试在胚胎肠道中发现的其他转录因子缺失的后果，我们开发了一种只在肠道中对RNAi敏感的蠕虫株；然而，我们无法(除了一个可能的例外)确定任何其他转录因子的肠道功能丧失导致的表型与ELT-2缺失引起的表型相当的严重程度。总体而言，我们的结果支持这样一个模型，即ELT-2是后规范线虫肠道中的主要转录因子，并直接参与大多数(>；80%)肠道基因的转录调控。我们提供的证据表明ELT-2在线虫肠道生理的大部分方面都发挥着核心作用：建立肠道细胞的结构，调节参与消化和营养的酶和转运蛋白，响应环境毒素和病原体感染，以及调节影响衰老和寿命的daf-2/daf-16途径的下游肠道成分。
Starting with SAGE-libraries prepared from C. elegans FAC-sorted embryonic intestine cells (8E-16E cell stage), from total embryos and from purified oocytes, and taking advantage of the NextDB in situ hybridization data base, we define sets of genes highly expressed from the zygotic genome, and expressed either exclusively or preferentially in the embryonic intestine or in the intestine of newly hatched larvae; we had previously defined a similarly expressed set of genes from the adult intestine. We show that an extended TGATAA-like sequence is essentially the only candidate for a cis-acting regulatory motif common to intestine genes expressed at all stages. This sequence is a strong ELT-2 binding site and matches the sequence of GATA-like sites found to be important for the expression of every intestinal gene so far analyzed experimentally. We show that the majority of these three sets of highly expressed intestinal-specific/intestinal-enriched genes respond strongly to ectopic expression of ELT-2 within the embryo. By flow-sorting elt-2(null) larvae from elt-2(+) larvae and then preparing Solexa/Illumina-SAGE libraries, we show that the majority of these genes also respond strongly to loss-of-function of ELT-2. To test the consequences of loss of other transcription factors identified in the embryonic intestine, we develop a strain of worms that is RNAi-sensitive only in the intestine; however, we are unable (with one possible exception) to identify any other transcription factor whose intestinal loss-of-function causes a phenotype of comparable severity to the phenotype caused by loss of ELT-2. Overall, our results support a model in which ELT-2 is the predominant transcription factor in the post-specification C. elegans intestine and participates directly in the transcriptional regulation of the majority (> 80%) of intestinal genes. We present evidence that ELT-2 plays a central role in most aspects of C. elegans intestinal physiology: establishing the structure of the enterocyte, regulating enzymes and transporters involved in digestion and nutrition, responding to environmental toxins and pathogenic infections, and regulating the downstream intestinal components of the daf-2/daf-16 pathway influencing aging and longevity.
登录
查看更多内容
影响因子：
10.5
作者：
Horner, MA;Quintin, S;Mango, SE
通讯作者：
Mango, SE
秀丽隐杆线虫中不饱和脂肪酸组成的遗传调节。
影响因子：
4.5
作者：
Brock, Trisha J.;Browse, John;Watts, Jennifer L.
通讯作者：
Watts, Jennifer L.
影响因子：
64.5
作者：
Budovskaya YV;Wu K;Southworth LK;Jiang M;Tedesco P;Johnson TE;Kim SK
通讯作者：
Kim SK
影响因子：
2.7
作者：
Fukushige, T;Hawkins, MG;McGhee, JD
通讯作者：
McGhee, JD
影响因子：
5.3
作者：
Gilleard, JS;McGhee, JD
通讯作者：
McGhee, JD