Evolutionary rate heterogeneity of Alu repeats upstream of the APOA5 gene: do they regulate APOA5 expression?
Evolutionary rate heterogeneity of Alu repeats upstream of the APOA5 gene: do they regulate APOA5 expression?
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APOA5 基因上游 Alu 重复序列的进化速率异质性：它们是否调节 APOA5 表达？
DOI：
10.1007/s10038-008-0245-7
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发表时间：
2008
影响因子：
3.5
通讯作者：
Campos,Hannia
中科院分区：
文献类型：
--
作者：
Ruiz-Narváez,EdwardA;Campos,Hannia
The APOA5 gene, located in the APOA1/C3/A4/A5 gene cluster, is a key regulator of triglyceride metabolism. ApoAV plasma concentration is much lower as compared to other apolipoproteins such as apoCIII and apoAI. This is due in part to the fact that the APOC3-enhancer, which up-regulates transcription of the APOA1, APOC3, and APOA4 genes, does not increase expression of the APOA5 gene. We postulated that intervening Alu repeats in the APOA5-APOA4 intergenic region gene might be blocking action of the APOC3-enhancer over the APOA5-promoter. To search for evidence of functional significance of the intervening Alu sequences, we estimated nucleotide substitution rates of 21 pairs of Alu elements in the APOA5-APOA4 intergenic region by comparing published sequences of human and chimpanzee. Also, we scanned the intergenic region for the presence of binding sites of the insulator protein CTCF. Seven out of the nine found CTCF binding sites were located in the first half of the intergenic region. Five out of those seven CTCF binding sites were placed inside Alu elements. Based on their substitution rates, we found two clearly defined groups of Alu sequences: a slow-evolving group (mean 0.98±0.18) and a fast-evolving group (mean 2.74±0.54). Alu repeats with lower substitution rate tended to be located up to 14-kb upstream of the APOA5 gene, to belong to the oldest J-family and to have an opposite orientation to the APOA5 gene. Some Alu sequences may have functional relevance on the regulation of the APOA5-gene expression.
