基因表達調控的絕緣體元件
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下一篇 2012-03-23 14:50:42/ 個人分類：實驗方法
第一次看到這個名詞:insulator element(金山詞霸把它譯成絕緣體)
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.(提出問題:HIF binding
motif多,target少;順式作用元件多,調節的目標蛋白少) Here, we investigated the transcriptional
response of GYS1 and RUVBL2 genes to hypoxia to understand the mechanisms that
restrict HIF activity toward specific genes(以兩個具體的基因為研究模型). 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(特殊情況出現). Analysis of the
transcriptional response of chimeric constructs derived from the intergenic
region revealed an inhibitory sequence whose deletion allowed
RUVBL2 induction by HIF(發現inhibitory sequence,這個就是絕緣子). 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(進一步實驗). Hence,
in this model, the selective response to HIF is achieved with the aid of
insulator elements(為什么調節靶蛋白少了?因為順式作用元件后面接了個絕緣子,呵呵有點意思). This is
the first report suggesting a role for insulators in the regulation of
differential gene expression in response to environmental signals.
啟示:
根據這個例子基因間序列也可能是有功能的,所以圖位克隆的時候如果預測基因區無多態性,可以暫緩考慮跳樓.這個絕緣子估計目前用任何軟件都預測不出來.
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