The transcription factor ccaat/enhancer binding protein beta (C/EBP beta) and miR-27a regulate the expression of porcine Dickkopf2 (DKK2)

文献类型： 外文期刊

第一作者： Tao, Hu

作者： Tao, Hu;Wang, Lei;Zhou, Jiawei;Pang, Panfei;Cai, Shanzhi;Li, Jialian;Li, Fenge;Tao, Hu;Wang, Lei;Zhou, Jiawei;Pang, Panfei;Cai, Shanzhi;Li, Jialian;Li, Fenge;Tao, Hu;Mei, Shuqi;Li, Fenge

作者机构：

期刊名称：SCIENTIFIC REPORTS （ 影响因子：4.379； 五年影响因子：5.133 ）

ISSN： 2045-2322

年卷期： 2015 年 5 卷

页码：

收录情况： SCI

摘要： Using Affymetrix porcine Gene-Chip analyses, we found that Dickkopf2 (DKK2), a WNT antagonist, is differentially expressed in pre-ovulatory follicles between Large White and Chinese Taihu sows. This study aims to identify the regulatory factors responsible for DKK2 expression. Deletion fragment and mutation analyses identified DKK2-D3 as the porcine DKK2 core promoter. There were four C/EBP beta binding sites within the DKK2 core promoter. The C allele that results from a spontaneous alteration (DKK2 c.-1130 T>C) in the core promoter was associated with a higher total number born (TNB) and a higher number born alive (NBA) in all parities in a synthetic pig population. This was possibly the result of a change in C/EBP beta binding ability, which was confirmed using chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assays (EMSA). Moreover, C/EBP beta specifically bound to and activated the DKK2 promoter, as revealed by mutation analysis, overexpression and RNA interference (RNAi) experiments. We also confirmed that miR-27a is a negative regulator of the DKK2 gene using miR-27a overexpression and inhibition experiments and mutation analyses. RTCA x CELLigence experiments showed that miR-27a suppressed Chinese hamster ovary (CHO) cell proliferation by down-regulating DKK2 gene expression. Taken together, our findings suggest that C/EBP beta and miR-27a control DKK2 transcription.

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