Identification of transcription factors and single nucleotide polymorphisms of Lrh1 and its homologous genes in Lrh1-knockout pancreas of mice

Background: 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. Methods: 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. Results: 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. Conclusion: 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.