Abstract

BackgroundTo identify transcription factors (TFs) and single nucleotide polymorphisms (SNPs) of Lrh1 (also named Nr5a2) and its homologous genes in Lrh1-knockout pancreas of mice.MethodsThe 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.ResultsTotal 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.ConclusionFTF 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.

Highlights

  • To identify transcription factors (TFs) and single nucleotide polymorphisms (SNPs) of Liver receptor homolog-1 (Lrh1) and its homologous genes in Lrh1-knockout pancreas of mice

  • Function and pathway annotation of Lrh1 homologous genes To determine the function of Lrh1 homologous genes in pancreas, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to analyze the up- and down-regulated Lrh1 homologous genes

  • For function and pathway annotation, differentially expressed genes (DEGs) were enriched into hexose metabolic process and monosaccharide metabolic process, which were involved into glycometabolism (Figure 1)

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Summary

Introduction

To identify transcription factors (TFs) and single nucleotide polymorphisms (SNPs) of Lrh ( named Nr5a2) and its homologous genes in Lrh1-knockout pancreas of mice. The pancreas is an endocrine gland, producing insulin, glucagon, somatostatin, and pancreatic polypeptide, and an exocrine gland, accounting for more than 98% of pancreatic gland and secreting pancreatic juice containing digestive enzymes [1]. These digestive enzymes help to further break down the carbohydrates, proteins and. Fayard E et al [6] have demonstrated that both Lrh and CEL (encoding carboxyl ester lipase) are co-expressed and confined to the exocrine pancreas. Lrh is a downstream target in the PDX-1 (lead to pancreas agenesis) regulatory cascade that is activated only during early stages of pancreas development and that governs pancreatic development, differentiation and function [8]

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