Transcriptional regulation of BMP4 synexpression in transgenic Xenopus
Transcriptional regulation of BMP4 synexpression in transgenic Xenopus
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DOI：
10.1038/sj.emboj.7600101
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发表时间：
2004-02-25
期刊：
影响因子：
11.4
通讯作者：
Niehrs, C
中科院分区：
文献类型：
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作者：
Karaulanov, E;Knöchel, W;Niehrs, C
共表达组是由基因组成的遗传模块，这些基因共享复杂的表达模式和它们发挥功能的生物过程。在这里，我们调查BMP 4的同向表达的调节，通过研究的增强子bambi，smad 7和vent 2在非洲爪蟾。我们发现BMP 4同功表达启动子模块很紧凑，并且（i）通过Smad和Smad辅因子结合基序需要直接的BMP响应，（ii）可能包含进化上保守的BMP响应元件bre 7（TGGCGCC），这对于bambi和smad 7的表达至关重要，并且对于新型BMP响应增强子（BREs）具有高度预后性;和（iii）需要BMP诱导的窄窗口，因为BMP反应性的微小增强或降低消除了同基因表达。此外，我们使用生物信息学模型预测了13种新的BREs，并测试了其中5种在id 1 -4基因中发现的BREs。结果强调，需要在体内分析，以揭示BMP响应基因的生理，时空调控。
Synexpression groups are genetic modules composed of genes that share both a complex expression pattern and the biological process in which they function. Here we investigate the regulation of BMP4 synexpression by studying the enhancers of bambi, smad7 and vent2 in Xenopus. We find that a BMP4 synexpression promoter module is compact and (i) requires direct BMP responsiveness through Smad and Smad-cofactor binding motifs, (ii) may contain an evolutionary conserved BMP-responsive element, bre7 (TGGCGCC), that is crucial for expression of bambi and smad7 and is highly prognostic for novel BMP-responsive enhancers (BREs); and (iii) requires a narrow window of BMP inducibility, because minor enhancement or reduction of BMP responsiveness abolishes synexpression. Furthermore, we used a bioinformatic model to predict in silico 13 novel BREs, and tested five of them that were found in the id1-4 genes. The results highlight that in vivo analysis is required to reveal the physiological, spatio-temporal regulation of BMP-responsive genes.