基因表达调控的绝缘体元件
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下一篇 2012-03-23 14:50:42/ 个人分类：实验方法
第一次看到这个名词:insulator element(金山词霸把它译成绝缘体)
A role for insulator elements in the regulation of gene
expression response to hypoxia
Nucl. Acids Res. (2012) 40(5): 1916-1927
first published online November 8, 2011 doi:10.1093/nar/gkr842
摘要:Hypoxia inducible factor (HIF) up-regulates the
transcription of a few hundred genes required for the adaptation to hypoxia.
This restricted set of targets is in sharp contrast with the widespread
distribution of the HIF binding motif throughout the genome.(提出问题:HIF binding
motif多,target少;顺式作用元件多,调节的目标蛋白少) Here, we investigated the transcriptional
response of GYS1 and RUVBL2 genes to hypoxia to understand the mechanisms that
restrict HIF activity toward specific genes(以两个具体的基因为研究模型). GYS1 and RUVBL2
genes are encoded by opposite DNA strands and separated by a short intergenic
region (~1 kb) that contains a functional hypoxia
response element equidistant to both genes. However, hypoxia
induced the expression of GYS1 gene only(特殊情况出现). Analysis of the
transcriptional response of chimeric constructs derived from the intergenic
region revealed an inhibitory sequence whose deletion allowed
RUVBL2 induction by HIF(发现inhibitory sequence,这个就是绝缘子). Enhancer blocking
assays, performed in cell culture and transgenic zebrafish, confirmed the
existence of an insulator element within this inhibitory region that could
explain the differential regulation of GYS1 and RUVBL2 by hypoxia(进一步实验). Hence,
in this model, the selective response to HIF is achieved with the aid of
insulator elements(为什么调节靶蛋白少了?因为顺式作用元件后面接了个绝缘子,呵呵有点意思). This is
the first report suggesting a role for insulators in the regulation of
differential gene expression in response to environmental signals.
启示:
根据这个例子基因间序列也可能是有功能的,所以图位克隆的时候如果预测基因区无多态性,可以暂缓考虑跳楼.这个绝缘子估计目前用任何软件都预测不出来.
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