Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No,301, Yanchang Middle Road, Shanghai 200072, China.
BMC Med Genet. 2014 Apr 15;15:43. doi: 10.1186/1471-2350-15-43.
To identify transcription factors (TFs) and single nucleotide polymorphisms (SNPs) of Lrh1 (also named Nr5a2) and its homologous genes in Lrh1-knockout pancreas of mice.
The RNA-Seq data GSE34030 were downloaded from Gene Expression Omnibus (GEO) database, including 2 Lrh1 pancreas knockout samples and 2 wild type samples. All reads were processed through TopHat and Cufflinks package to calculate gene-expression level. Then, the differentially expressed genes (DEGs) were identified via non-parametric algorithm (NOISeq) methods in R package, of which the homology genes of Lrh1 were identified via BLASTN analysis. Furthermore, the TFs of Lrh1 and its homologous genes were selected based on TRANSFAC database. Additionally, the SNPs were analyzed via SAM tool to record the locations of mutant sites.
Total 15683 DEGs were identified, of which 23 was Lrh1 homology genes (3 up-regulated and 20 down-regulated). Fetoprotein TF (FTF) was the only TF of Lrh1 identified and the promoter-binding factor of FTF was CYP7A. The SNP annotations of Lrh1 homologous genes showed that 92% of the mutation sites were occurred in intron and upstream. Three SNPs of Lrh1 were located in intron, while 1819 SNPs of Phkb were located in intron and 1343 SNPs were located in the upstream region.
FTF combined with CYP7A might play an important role in Lrh1 regulated pancreas-specific transcriptional network. Furthermore, the SNPs analysis of Lrh1 and its homology genes provided the candidate mutant sites that might affect the Lrh1-related production and secretion of pancreatic fluid.
鉴定 Lrh1（也称为 Nr5a2）及其同源基因在 Lrh1 敲除小鼠胰腺中的转录因子（TFs）和单核苷酸多态性（SNPs）。
从基因表达综合（GEO）数据库中下载 RNA-Seq 数据 GSE34030，包括 2 个 Lrh1 胰腺敲除样本和 2 个野生型样本。所有读取均通过 TopHat 和 Cufflinks 软件包进行处理，以计算基因表达水平。然后，通过 R 包中的非参数算法（NOISeq）方法识别差异表达基因（DEGs），其中 Lrh1 的同源基因通过 BLASTN 分析进行鉴定。此外，根据 TRANSFAC 数据库选择 Lrh1 及其同源基因的 TF。另外，通过 SAM 工具分析 SNPs，记录突变位点的位置。
总共鉴定出 15683 个 DEGs，其中 23 个是 Lrh1 同源基因（3 个上调，20 个下调）。胎蛋白 TF（FTF）是唯一鉴定出的 Lrh1 TF，FTF 的启动子结合因子是 CYP7A。Lrh1 同源基因的 SNP 注释显示，92%的突变位点发生在内含子和上游。Lrh1 的 3 个 SNP 位于内含子中，而 Phkb 的 1819 个 SNP 位于内含子中，1343 个 SNP 位于上游区域。
FTF 与 CYP7A 结合可能在 Lrh1 调节的胰腺特异性转录网络中发挥重要作用。此外，Lrh1 及其同源基因的 SNPs 分析提供了可能影响 Lrh1 相关胰腺液产生和分泌的候选突变位点。
